Showing papers in "Journal of orthopaedic translation in 2022"
TL;DR: In this article , the authors comprehensively analyzed the global level and trends of prevalence, incidence and years lived with disability for low back pain (LBP) from 1990 to 2019 by age, sex and sociodemographic index (SDI).
Abstract: To comprehensively analyze the global level and trends of prevalence, incidence and years lived with disability (YLDs) for low back pain (LBP) from 1990 to 2019 by age, sex and sociodemographic index (SDI). Publicly available modelled data and methods were obtained from the Global Burden of Diseases (GBD) study 2019, and used to evaluate the global burden of LBP through a systematic analysis. Globally, the age-standardized prevalence, incidence and YLDs rate of LBP were slightly decreased from 1990 to 2019, but the number of the prevalent cases, incident cases and YLDs had substantially increased, and LBP remains the leading cause of YLDs in 2019 worldwide. The number of prevalent cases was increased with age and peaked at the age of 45–54 years for both sexes, and the global prevalence rate was higher in females than in males and increased with age, peaking at the 80–84 age group in both sexes in 2019. Overall, a positive association between the age-standardized YLD rate and SDI was observed over the past thirty years. At the national revel, the United States, Denmark and Switzerland had the three highest levels of age-standardized prevalence, while Zambia, Zimbabwe and Canada showed the highest increase in the age-standardized prevalence during 1990–2019. LBP is a major public health issue globally, and its burden remains high. Increasing population awareness about its risk factors and preventive measures for LBP are needed to reduce the future burden of this condition. Due to the high prevalence and heavy burden of LBP globally, it is important to update its epidemiological data. This systematic analysis provides researchers and healthcare policy makers with up-to-date, comprehensive and comparable information on global LBP burden, which is of clinical translational significance.
68 citations
TL;DR: In this article, the authors comprehensively analyzed the global level and trends of prevalence, incidence and years lived with disability (YLDs) for low back pain (LBP) from 1990 to 2019 by age, sex and sociodemographic index (SDI).
Abstract: Background To comprehensively analyze the global level and trends of prevalence, incidence and years lived with disability (YLDs) for low back pain (LBP) from 1990 to 2019 by age, sex and sociodemographic index (SDI). Methods Publicly available modelled data and methods were obtained from the Global Burden of Diseases (GBD) study 2019, and used to evaluate the global burden of LBP through a systematic analysis. Results Globally, the age-standardized prevalence, incidence and YLDs rate of LBP were slightly decreased from 1990 to 2019, but the number of the prevalent cases, incident cases and YLDs had substantially increased, and LBP remains the leading cause of YLDs in 2019 worldwide. The number of prevalent cases was increased with age and peaked at the age of 45–54 years for both sexes, and the global prevalence rate was higher in females than in males and increased with age, peaking at the 80–84 age group in both sexes in 2019. Overall, a positive association between the age-standardized YLD rate and SDI was observed over the past thirty years. At the national revel, the United States, Denmark and Switzerland had the three highest levels of age-standardized prevalence, while Zambia, Zimbabwe and Canada showed the highest increase in the age-standardized prevalence during 1990–2019. Conclusions LBP is a major public health issue globally, and its burden remains high. Increasing population awareness about its risk factors and preventive measures for LBP are needed to reduce the future burden of this condition. The translational potential of this article Due to the high prevalence and heavy burden of LBP globally, it is important to update its epidemiological data. This systematic analysis provides researchers and healthcare policy makers with up-to-date, comprehensive and comparable information on global LBP burden, which is of clinical translational significance.
68 citations
TL;DR: The periosteum plays a significant role in bone formation and regeneration by storing progenitor cells, and also acts as a source of local growth factors and a scaffold for recruiting cells and other growth factors as mentioned in this paper .
Abstract: Periosteum plays a significant role in bone formation and regeneration by storing progenitor cells, and also acts as a source of local growth factors and a scaffold for recruiting cells and other growth factors. Recently, tissue-engineered periosteum has been studied extensively and shown to be important for osteogenesis and chondrogenesis. Using biomimetic methods for artificial periosteum synthesis, membranous tissues with similar function and structure to native periosteum are produced that significantly improve the efficacy of bone grafting and scaffold engineering, and can serve as direct replacements for native periosteum. Many problems involving bone defects can be solved by preparation of idealized periosteum from materials with different properties using various techniques.This review summarizes the significance of periosteum for osteogenesis and chondrogenesis from the aspects of periosteum tissue structure, osteogenesis performance, clinical application, and development of periosteum tissue engineering. The advantages and disadvantages of different tissue engineering methods are also summarized.The fast-developing field of periosteum tissue engineering is aimed toward synthesis of bionic periosteum that can ensure or accelerate the repair of bone defects. Artificial periosteum materials can be similar to natural periosteum in both structure and function, and have good therapeutic potential. Induction of periosteum tissue regeneration and bone regeneration by biomimetic periosteum is the ideal process for bone repair.Periosteum is essential for bone formation and regeneration, and it is indispensable in bone repair. Achieving personalized structure and composition in the construction of tissue engineering periosteum is in accordance with the design concept of both universality and emphasis on individual differences and ensures the combination of commonness and individuality, which are expected to meet the clinical needs of bone repair more effectively.To better understand the role of periosteum in bone repair, clarify the present research situation of periosteum and tissue engineering periosteum, and determine the development and optimization direction of tissue engineering periosteum in the future. It is hoped that periosteum tissue engineering will play a greater role in meeting the clinical needs of bone repair in the future, and makes it possible to achieve optimization of bone tissue therapy.
38 citations
TL;DR: This review article summarized current findings of signaling pathways involved in TMJ OA, including Wnt/β-catenin, TGF-β and BMP, Indian Hedgehog, FGF, NF-κB, and Notch pathways, to better understand the pathological mechanisms of TMj OA and define the molecular targets for TM J OA treatment.
Abstract: Objective Temporomandibular joint (TMJ) osteoarthritis (OA) is a type of TMJ disorders with clinical symptoms of pain, movement limitation, cartilage degeneration and joint dysfunction. This review article is aiming to summarize recent findings on signaling pathways involved in TMJ OA development and progression. Methods Most recent findings in TMJ OA studies have been reviewed and cited. Results TMJ OA is caused by inflammation, abnormal mechanical loading and genetic abnormalities. The molecular mechanisms related to TMJ OA have been determined using different genetic mouse models. Recent studies demonstrated that several signaling pathways are involved in TMJ OA pathology, including Wnt/β-catenin, TGF-β and BMP, Indian Hedgehog, FGF, NF-κB, and Notch pathways, which are summarized in this review article. Alterations of these signaling pathways lead to the pathological changes in TMJ tissues, affecting cartilage matrix degradation, catabolic metabolism and chondrocyte apoptosis. Conclusion Multiple signaling pathways were involved in the pathological process of TMJ OA. New therapeutic strategies, such as stem cell application, gene editing and other techniques may be utilized for TMJ OA treatment. The translational potential of this article TMJ OA is a most important subtype of TMJ disorders and may lead to substantial joint pain, dysfunction, dental malocclusion, and reduced health-related quality of life. This review article summarized current findings of signaling pathways involved in TMJ OA, including Wnt/β-catenin, TGF-β and BMP, Indian Hedgehog, FGF, NF-κB, and Notch pathways, to better understand the pathological mechanisms of TMJ OA and define the molecular targets for TMJ OA treatment.
25 citations
TL;DR: This study demonstrates an essential role of Kinlind-2 expression in osteoprogenitors in regulating skeletogenesis and bone mass accrual and homeostasis in mice and may define a novel therapeutic target for treatment of skeletal diseases, such as chondrodysplasia and osteoporosis.
Abstract: Background Our recent studies demonstrate that the focal adhesion protein Kindlin-2 exerts crucial functions in the mesenchymal stem cells, mature osteoblasts and osteocytes in control of early skeletal development and bone homeostasis in mice. However, whether Kindlin-2 plays a role in osteoprogenitors remains unclear. Materials and methods Mice lacking Kindlin-2 expression in osterix (Osx)-expressing cells (i.e., osteoprogenitors) were generated. Micro-computerized tomography (μCT) analyses, histology, bone histomorphometry and immunohistochemistry were performed to determine the effects of Kindlin-2 deletion on skeletal development and bone mass accrual and homeostasis. Bone marrow stromal cells (BMSCs) from mutant mice (Kindlin-2fl/fl; OsxCre) and control littermates were isolated and determined for their osteoblastic differentiation capacity. Results Kindlin-2 was highly expressed in osteoprogenitors during endochondral ossification. Deleting Kindlin-2 expression in osteoprogenitors impaired both intramembranous and endochondral ossifications. Mutant mice displayed multiple severe skeletal abnormalities, including unmineralized fontanel, limb shortening and growth retardation. Deletion of Kindlin-2 in osteoprogenitors impaired the growth plate development and largely delayed formation of the secondary ossification center in the long bones. Furthermore, adult mutant mice displayed a severe low-turnover osteopenia with a dramatic decrease in bone formation which exceeded that in bone resorption. Primary BMSCs isolated from mutant mice exhibited decreased osteoblastic differentiation capacity. Conclusions Our study demonstrates an essential role of Kinlind-2 expression in osteoprogenitors in regulating skeletogenesis and bone mass accrual and homeostasis in mice. The translational potential of this article This study reveals that Kindlin-2 through its expression in osteoprogenitor cells controls chondrogenesis and bone mass. We may define a novel therapeutic target for treatment of skeletal diseases, such as chondrodysplasia and osteoporosis.
18 citations
TL;DR: Kindlin-2 was highly expressed in osteoprogenitors during endochondral ossification, and deletion of this protein impaired bone formation and bone mass accrual and homeostasis as discussed by the authors .
Abstract: Our recent studies demonstrate that the focal adhesion protein Kindlin-2 exerts crucial functions in the mesenchymal stem cells, mature osteoblasts and osteocytes in control of early skeletal development and bone homeostasis in mice. However, whether Kindlin-2 plays a role in osteoprogenitors remains unclear.Mice lacking Kindlin-2 expression in osterix (Osx)-expressing cells (i.e., osteoprogenitors) were generated. Micro-computerized tomography (μCT) analyses, histology, bone histomorphometry and immunohistochemistry were performed to determine the effects of Kindlin-2 deletion on skeletal development and bone mass accrual and homeostasis. Bone marrow stromal cells (BMSCs) from mutant mice (Kindlin-2fl/fl; OsxCre ) and control littermates were isolated and determined for their osteoblastic differentiation capacity.Kindlin-2 was highly expressed in osteoprogenitors during endochondral ossification. Deleting Kindlin-2 expression in osteoprogenitors impaired both intramembranous and endochondral ossifications. Mutant mice displayed multiple severe skeletal abnormalities, including unmineralized fontanel, limb shortening and growth retardation. Deletion of Kindlin-2 in osteoprogenitors impaired the growth plate development and largely delayed formation of the secondary ossification center in the long bones. Furthermore, adult mutant mice displayed a severe low-turnover osteopenia with a dramatic decrease in bone formation which exceeded that in bone resorption. Primary BMSCs isolated from mutant mice exhibited decreased osteoblastic differentiation capacity.Our study demonstrates an essential role of Kinlind-2 expression in osteoprogenitors in regulating skeletogenesis and bone mass accrual and homeostasis in mice.This study reveals that Kindlin-2 through its expression in osteoprogenitor cells controls chondrogenesis and bone mass. We may define a novel therapeutic target for treatment of skeletal diseases, such as chondrodysplasia and osteoporosis.
17 citations
TL;DR: Puerarin, a unique C-glycoside isoflavonoid, was found to be able to prevent bone loss by inhibiting bone resorption, but the underlying mechanism was controversial as discussed by the authors .
Abstract: Given the limitations of current anti-resorption agents for postmenopausal osteoporosis, there is a need for alternatives without impairing coupling crosstalk between bone resorption and bone formation ie. osteoclastogenesis. Puerarin, a unique C-glycoside isoflavonoid, was found to be able to prevent bone loss by inhibiting bone resorption, but the underlying mechanism was controversial. In this study, we investigated the effects of puerarin on osteoclastic differentiation, activation and bone resorption and its underlying molecular mechanism in vitro, and then evaluated the effects of puerarin on bone metabolism using an ovariectomized (OVX) rat model.In vitro, the effect of puerarin on osteoclastic cytotoxicity, differentiation, apoptosis, activation and function were studied in raw 264.7 cells and mouse BMMs. Mechanistically, osteoclast-related makers were determined by RT-PCR, western blot, immunofluorescence, and kinase activity assay. In vivo, Micro-CT, histology, serum bone biomarker, and mechanical testing were used to evaluate the effects of puerarin on preventing osteoporosis.Puerarin significantly inhibited osteoclast activation and bone resorption, without affecting osteoclastogenesis or apoptosis. In terms of mechanism, the expressions of protein of integrin-β3 and phosphorylations of Src, Pyk2 and Cbl were lower in puerarin group than those in the control group. Oral administration of puerarin prevented OVX-induced trabecular bone loss and significantly improved bone strength in rats. Moreover, puerarin significantly decreased trap positive osteoclast numbers and serum TRAP-5b, CTx1, without affecting bone formation rate.Collectively, puerarin prevented the bone loss in OVX rat through suppression of osteoclast activation and bone resorption, by inhibiting integrin-β3-Pyk2/Cbl/Src signaling pathway, without affecting osteoclasts formation or apoptosis.These results demonstrate the unique mechanism of puerarin on bone metabolism and provide a novel agent for prevention of postmenopausal osteoporosis.
17 citations
TL;DR: A mussel-inspired strategy was developed to construct an ECM-mimicking hydrogel scaffold by incorporating polydopamine-modified hyaluronic acid (PDA/HA) complex into a dual-crosslinked collagen (Col) matrix for growth factor-free cartilage regeneration as discussed by the authors .
Abstract: Injury to articular cartilage cause certain degree of disability due to poor self-repair ability of cartilage tissue. To promote cartilage regeneration, it is essential to develop a scaffold that properly mimics the native cartilage extracellular matrix (ECM) in the aspect of compositions and functions.A mussel-inspired strategy was developed to construct an ECM-mimicking hydrogel scaffold by incorporating polydopamine-modified hyaluronic acid (PDA/HA) complex into a dual-crosslinked collagen (Col) matrix for growth factor-free cartilage regeneration. The adhesion, proliferation, and chondrogenic differentiation of cells on the scaffold were examined. A well-established full-thickness cartilage defect model of the knee in rabbits was used to evaluated the efficacy and functionality of the engineered Col/PDA/HA hydrogel scaffold.The PDA/HA complex incorporated-hydrogel scaffold with catechol moieties exhibited better cell affinity than bare negatively-charged HA incorporated hydrogel scaffold. In addition, the PDA/HA complex endowed the scaffold with immunomodulation ability, which suppressed the expression of inflammatory cytokines and effectively activated the polarization of macrophages toward M2 phenotypes. The in vivo results revealed that the mussel-inspired Col/PDA/HA hydrogel scaffold showed strong cartilage inducing ability to promote cartilage regeneration.The PDA/HA complex-incorporated hydrogel scaffold overcame the cell repellency of negatively-charged polysaccharide-based scaffolds, which facilitated the adhesion and clustering of cells on the scaffold, and therefore enhanced cell-HA interactions for efficient chondrogenic differentiation. Moreover, the hydrogel scaffold modulated immune microenvironment, and created a regenerative microenvironment to enhance cartilage regeneration.This study gives insight into the mussel-inspired approach to construct the tissue-inducing hydrogel scaffold in a growth-factor-free manner, which show great advantage in the clinical treatment. The hydrogel scaffold composed of collagen and hyaluronic acid as the major component, providing cartilage ECM-mimicking environment, is promising for cartilage defect repair.
16 citations
TL;DR: In this paper , a glycerol cross-linked PVA gel (GPG) was synthesized based on multiple H-bonds formation between GPG molecules and PVA chains for intervertebral disc lesion repair.
Abstract: Intervertebral disc (IVD) degeneration (IVDD) that greatly affected by regional biomechanical environment is a major cause of low back pain. Injectable hydrogels have been commonly studied for treatment of IVDD due to their capability of mimicking extracellular matrix structure to support cellular behavior and clinical prospects in minimally invasive treatment. However, most hydrogels suffer from complicated chemistry, potential uncertainty and toxicity from in-situ gelation, and mismatch with IVD mechanical environment that limit their therapeutic effects or clinical translation in IVDD or intervertebral disc defect repair. For IVD lesion repair, the study aims to develop a novel hydrogel with shear-thinning enabled injectability, high bio-safety, and mechanical properties adaptable to the IVD environment, using a simple chemistry and method. And therapeutic efficacy of the novel hydrogel in the treatment of IVDD or intervertebral disc defect will be revealed.A glycerol cross-linked PVA gel (GPG) was synthesized based on multiple H-bonds formation between glycerol molecules and PVA chains. The rheological and mechanical properties were tested. The swelling ratio was measured. The micro-architecture was observed through scanning and transmission electron microscopes. Nucleus pulposus (NP) cells were cultured in GPG-coated plates or silicone chambers treated under hydrostatic or dynamic loading in vitro, and examined for proliferation, vitality, apoptosis, expression of catabolic and anabolic markers. GPG was injected in needle puncture (IDD) or NP discectomy (NPD) models in vivo, and examined through magnetic resonance imaging, micro-computed tomography scanning and histological staining.GPG had a highly porous structure consisting of interconnected pores. Meanwhile, the GPG had NP-like viscoelastic property, and was able to withstand the cyclic deformation while exhibiting a prominent energy-dissipating capability. In vitro cell tests demonstrated that, the hydrogel significantly down-regulated the expression of catabolic markers, maintained the level of anabolic markers, preserved cell proliferation and vitality, reduced apoptotic rate of NP cells under pathologically hydrostatic and dynamic loading environments compared to cells cultured on untreated plate or silicone chamber. In vivo animal studies revealed that injection of GPG efficiently maintained NP structural integrity, IVD height and relative water content in IDD models, and stimulated the fibrous repair in NPD models.This study showed that GPG, with high injectability, NP-like viscoelastic characteristics, good energy-dissipating properties and swelling capacities, preserved NP cells vitality against pathological loading, and had therapeutic effects on IVD repair in IDD and NPD models.Effective clinical strategy for treatment of intervertebral disc degeneration (IVDD) is still lacking. This study demonstrates that injection of a hydrogel with nucleus pulposus-matched viscoelastic property could remarkably prevent the IVDD progress. Prepared with simple chemistry and procedure, the cell/drug-free GPG with high bio-safety and shear-thinning enabled injectability bears great translational potential for the clinical treatment of IVDD via a minimally invasive approach.
15 citations
TL;DR: A systematic review of the orthopedic guide template is presented in this article , where the history of 3D-printing-guided technology, the process of guides, and basic clinical applications are described.
Abstract: With increasing requirements for medical effects, and huge differences among individuals, traditional surgical instruments are difficult to meet the patients' growing medical demands. 3D printing is increasingly mature, which connects to medical services critically as well. The patient specific surgical guide plate provides the condition for precision medicine in orthopaedics.In this paper, a systematic review of the orthopedic guide template is presented, where the history of 3D-printing-guided technology, the process of guides, and basic clinical applications of orthopedic guide templates are described. Finally, the limitations of the template and possible future directions are discussed.The technology of 3D printing surgical templates is increasingly mature, standard, and intelligent. With the help of guide templates, the surgeon can easily determine the direction and depth of the screw path, and choose the angle and range of osteotomy, increasing the precision, safety, and reliability of the procedure in various types of surgeries. It simplifies the difficult surgical steps and accelerates the growth of young and mid-career physicians. But some problems such as cost, materials, and equipment limit its development.In different fields of orthopedics, the use of guide templates can significantly improve surgical accuracy, shorten the surgical time, and reduce intraoperative bleeding and radiation. With the development of 3D printing, the guide template will be standardized and simplified from design to production and use. 3D printing guides will be further sublimated in the application of orthopedics and better serve the patients.Precision, intelligence, and individuation are the future development direction of orthopedics. It is more and more popular as the price of printers falls and materials are developed. In addition, the technology of meta-universe, digital twin, and artificial intelligence have made revolutionary effects on template guides. We aim to summarize recent developments and applications of 3D printing guide templates for engineers and surgeons to develop more accurate and efficient templates.
14 citations
TL;DR: An intimate relationship between hypertension and structural damages of knee OA is indicated, rather than simply chronic joint pain, especially in women, which provides stronger support for further investigations into the causal risk factor, i.e. hypertension.
Abstract: Objective Literature examining the relationship between elevated blood pressure and osteoarthritis (OA) has yielded conflicting results. This study aimed to systematically review the relationship between hypertension and OA in both load-bearing and non-load-bearing joints. Methods A systematic literature search was performed on Embase, Emcare, MEDLINE and Ovid Nursing Database. The associations between hypertension and OA development in knees, hips and hands were analysed by calculating the odds ratio (OR). Results A total of 26 studies with 97,960 participants were included. The overall odds of having OA significantly increased in the people with hypertension compared to the normotensive ones (OR = 1.60, 95%CI = 1.33, 1.94). The association of hypertension with OA was detected in knee (OR = 1.62, 95%CI = 1.32, 1.98), not in hand (OR = 1.19, 95%CI = 0.92, 1.53). Moreover, there existed a stronger association of hypertension with radiographic knee OA (OR = 1.89, 95%CI = 1.40, 2.54) than symptomatic knee OA (OR = 1.39, 95%CI = 1.17, 1.65). The association between hypertension and radiographic knee OA remained statistically significant for the studies that adjusted for body mass index (BMI) (OR = 1.42, 95%CI = 1.13, 1.78), and was particularly strong in women (OR = 2.27, 95%CI = 1.17, 4.39). Conclusion A BMI-independent association between hypertension and radiographic knee OA existed with potential sex variation, which warrants further investigations into the underlying genetic, hormonal and environmental factors. The translational potential of this article: Blood pressure has been reported to link with OA for years ago, however, its contribution to OA is still unclear and conflicted in different reports. This review indicated an intimate relationship between hypertension and structural damages of knee OA, rather than simply chronic joint pain, especially in women. This finding not only provides stronger support for further investigations into the causal risk factor, i.e. hypertension, of OA from tissue level to molecular level, but also putting forward a novel thinking in OA pathogenesis and its therapy strategies. Orthopedic translation This study further strengthen the association between hypertension and radiographic knee OA. It points in a vascular aetiology hypothesis of OA. It might open up a new avenue for repositioning anti-hypertensive medications for osteoarthritis treatment.
TL;DR: Wang et al. as discussed by the authors compared the radiologic and clinical outcomes of HURWA robotic-assisted total knee arthroplasty (TKA) to those of conventional TKA.
Abstract: The objective of this study was to compare the radiologic and clinical outcomes of HURWA robotic-assisted total knee arthroplasty (TKA) to those of conventional TKA.A total of 150 patients were randomized into two groups - 73 and 77 patients underwent robotic-assisted TKA and conventional TKA, respectively. Preoperative and postoperative Western Ontario McMaster University Osteoarthritis Index (WOMAC) score, Hospital for Special Surgery (HSS) score, 36-item Short Form Health Survey (SF-36) score, Knee Society Score (KSS) and range of motion (ROM) were obtained and compared between these two groups. The preoperative and postoperative hip-knee-ankle (HKA) angle and the rate of HKA≤3° in the two groups were also compared.The postoperative mean HKA angle was 1.801° ± 1.608° of varus for the robotic-assisted TKA group and 3.017° ± 2.735° of varus for the conventional TKA group; these values were significantly different. The alignment rate for mechanical axis lower than 3° in the robotic-assisted TKA group and the conventional TKA group were 81.2% and 63.5%, respectively. Patients undergone robotic-assisted TKA or conventional TKA had similarly improved knee flexion and functional recovery reflected by WOMAC score, HSS score, SF-36 score and KSS.HURWA robotic-assisted TKA is a safe and effective, resulting in better alignment for mechanical axis than conventional TKA. The improvement in knee flexion and functional recovery after HURWA robotic-assisted TKA were similar to those after conventional TKA. However, longer follow-up is needed to determine whether the improved alignment of mechanical axis will produce better long-term clinical outcomes.Recently, the robotic-assisted TKA system has been introduced to clinical practice for TKA. Several robotic-assisted TKA systems, including CASPAR, Tsolution, ROSA, ROBODOC and Mako, have been implemented into clinical application.However, the clinical application of these robotic systems was limited due to their technical complexity, insufficient versatility and increased operative time. Until now, there are still no robotic-assisted TKA systems approved by the National Medical Products Administration of China. Therefore, more robotic-assisted TKA systems need to be designed and improved, particularly in China. Through our randomized, multicenter, single blind and parallel controlled trial, we showed that HURWA robot-assisted TKA system is a safe and effective system for TKA, which had improved knee flexion.
TL;DR: In this article , a new treatment strategy of scaffold-guided bone regeneration (SGBR) was developed to address the limitations of autologous bone graft (ABG) such as limited harvest volume as well as overly fast remodelling and resorption.
Abstract: Bone defects after trauma, infection, or tumour resection present a challenge for patients and clinicians. To date, autologous bone graft (ABG) is the gold standard for bone regeneration. To address the limitations of ABG such as limited harvest volume as well as overly fast remodelling and resorption, a new treatment strategy of scaffold-guided bone regeneration (SGBR) was developed. In a well-characterized sheep model of large to extra-large tibial segmental defects, three-dimensional (3D) printed composite scaffolds have shown clinically relevant biocompatibility and osteoconductive capacity in SGBR strategies. Here, we report four challenging clinical cases with large complex posttraumatic long bone defects using patient-specific SGBR as a successful treatment. After giving informed consent computed tomography (CT) images were used to design patient-specific biodegradable medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP, 80:20 wt%) scaffolds. The CT scans were segmented using Materialise Mimics to produce a defect model and the scaffold parts were designed with Autodesk Meshmixer. Scaffold prototypes were 3D-printed to validate robust clinical handling and bone defect fit. The final scaffold design was additively manufactured under Food and Drug Administration (FDA) guidelines for patient-specific and custom-made implants by Osteopore International Pte Ltd. Four patients (age: 23–42 years) with posttraumatic lower extremity large long bone defects (case 1: 4 cm distal femur, case 2: 10 cm tibia shaft, case 3: complex malunion femur, case 4: irregularly shaped defect distal tibia) are presented. After giving informed consent, the patients were treated surgically by implanting a custom-made mPCL-TCP scaffold loaded with ABG (case 2: additional application of recombinant human bone morphogenetic protein-2) harvested with the Reamer-Irrigator-Aspirator system (RIA, Synthes®). In all cases, the scaffolds matched the actual anatomical defect well and no perioperative adverse events were observed. Cases 1, 3 and 4 showed evidence of bony ingrowth into the large honeycomb pores (pores >2 mm) and fully interconnected scaffold architecture with indicative osseous bridges at the bony ends on the last radiographic follow-up (8–9 months after implantation). Comprehensive bone regeneration and full weight bearing were achieved in case 2 at follow-up 23 months after implantation. This study shows the bench to bedside translation of guided bone regeneration principles into scaffold-based bone tissue engineering. The scaffold design in SGBR should have a tissue-specific morphological signature which stimulates and directs the stages from the initial host response towards the full regeneration. Thereby, the scaffolds provide a physical niche with morphology and biomaterial properties that allow cell migration, proliferation, and formation of vascularized tissue in the first one to two months, followed by functional bone formation and the capacity for physiological bone remodelling. Great design flexibility of composite scaffolds to support the one to three-year bone regeneration was observed in four patients with complex long bone defects. This study reports on the clinical efficacy of SGBR in the treatment of long bone defects. Moreover, it presents a comprehensive narrative of the rationale of this technology, highlighting its potential for bone regeneration treatment regimens in patients with any type of large and complex osseous defects.
TL;DR: In this paper , a porous magnesium scaffold was prepared by 3D gel printing and surface modification with an additional calcium phosphate coating and use of its strength, degradability and slow degradation rate in a bone graft substitute material.
Abstract: /Objective: The treatment of bone defect has always been a difficult problem in orthopedic clinic. The search for alternative biodegradable implants is a hot topic. The development of biodegradable magnesium scaffolds for the treatment of bone defects has long been a goal of the public.In this study, we proposed a porous magnesium scaffold prepared by 3D gel printing and surface modification with an additional calcium phosphate coating and use of its strength, degradability and slow degradation rate in a bone graft substitute material. The porous magnesium granular scaffold was prepared by 3D gel printing technology and modified by DCPD (Dibasic Calcium Phosphate Dihydrate) coating. The biocompatibility, degradation rate, and osteogenic ability of the scaffold were evaluated in vitro and in vivo.The biocompatibility, in vivo degradation and bone defect healing response of the implants were investigated. Porous magnesium scaffolds were successfully prepared, and the strength of sintered scaffolds reached 5.38 MPa. The degradation rates of scaffolds were significantly reduced after coating with DCPD. The cell compatibility evaluation showed that DCPD-coated Mg scaffold was suitable for cell proliferation. In vivo biosafety monitoring showed that scaffold implantation did not cause an increase in Mg ion concentration in vivo, and no toxic damage was detected in the liver or kidney. Micro-CT and pathological results showed that a large amount of new bone was formed at 6 weeks. At 12 weeks, approximately 52% of the scaffold volume remained. At 24 weeks, osteogenesis, which was stimulated by some residual scaffold, still can be observed. In summary, this study suggests that 3D gel-printed DCPD-coated porous magnesium scaffolds have great potential as bone graft alternatives.In summary, this study suggests that 3D gel-printed DCPD-coated porous magnesium scaffolds have great potential as bone graft alternatives.The translational potential of this article is to make use of the advantages of 3D gel printing technology with higher efficiency and lower cost compared with SLM and SLS technologies, and use pure magnesium powder as raw material to prepare degradable porous magnesium metal scaffolds, opening up a new technical route for the preparation of degradable porous magnesium scaffolds which are made for bone defect regeneration in the future.
TL;DR: A substantial amount of research is required on the relationship between imaging and histopathological features is required to further modify and revise the current wide-accepted classification systems of ONFH.
Abstract: Osteonecrosis of the femoral head (ONFH) is a recalcitrant ischemic disorder, which could be classified into two major categories: traumatic and nontraumatic. Regardless of different risk factors, it has been testified that ONFH results from primitive vascular problems, leading to temporary or permanent loss of blood supply to bone tissue. Histopathological and microarchitectural alterations ensues, which is a gradual evolutionary process involving bone marrow and osteocyte necrosis, progressive destruction of subchondral bone, unsuccessful reparative process, and eventual articular collapse and degenerative arthritis. Based on the imaging features of ONFH, different classification systems have been developed to evaluate the severity and prognosis of the disease, which is pivotal for implementation of treatment strategy, especially the joint-preserving surgery. However, patients classified with the same severity stage, especially in the peri-collapse stage, sometimes responded differently after similar joint-preserving surgery. The unusual phenomenon may be attributed to the limitation of the current imaging classification systems, which might underestimate the disease severity, especially when referring to the early stages. In this review, we briefly summarize the etiology and pathogenesis of ONFH. The imaging features and staging classification systems of ONFH are also described. More importantly, we focus on histopathological and microstructural alterations of the femoral head, and provide an overview of their essential contribution to ONFH progression. Given the observation of discordance between imaging characteristics and histopathological alterations, a substantial amount of research on the relationship between imaging and histopathological features is required to further modify and revise the current wide-accepted classification systems.
TL;DR: In this article , the authors investigated subchondral bone marrow lesions (BMLs) in knee OA patients who underwent total knee arthroplasty (TKA), and evaluated the associations of osteoclastogenesis and nerve growth.
Abstract: Subchondral bone marrow lesions (BMLs) are common magnetic resonance imaging (MRI) features in joints affected by osteoarthritis (OA), however, their clinical impacts and mechanisms remain controversial. Thus, we aimed to investigate subchondral BMLs in knee OA patients who underwent total knee arthroplasty (TKA), then evaluate the associations of osteoclastogenesis and nerve growth in subchondral BMLs with clinical symptoms.Total 70 patients with primary symptomatic knee OA were involved, then separated into three groups based on MRI (without BMLs group, n = 14; BMLs without cyst group, n = 37; BMLs with cyst group, n = 19). Volume of BMLs and cyst-like lesions was calculated via the OsiriX system. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was used to assess clinical symptoms. Histology and immunohistochemistry were deployed to assess subchondral osteoclastogenesis and nerve distribution. Pearson's correlation coefficient was used to evaluate the associations between volume of BMLs and joint symptoms, and to assess the associations of osteoclastogenesis and nerve growth in subchondral BMLs with joint symptoms.In BMLs combined with cyst group, patients exhibited increased osteoclastogenesis and nerve distribution in subchondral bone, as shown by increased expression of tartrate resistant acid phosphatase (TRAP) and protein gene product 9.5 (PGP9.5). Volume of subchondral cyst-like component was associated with joint pain (p < 0.05). Subchondral osteoclastogenesis and nerve distribution were positively associated with joint pain in BMLs with cyst group (p < 0.05).The subchondral cyst-like lesion was an independent factor for inducing pain in OA patients; osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for this joint pain.Our results indicated that the increased osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for the pain of OA joints. These findings may provide valuable basis for the treatment of OA.
TL;DR: In this article , a systematic literature search was performed on Embase, Emcare, MEDLINE and Ovid Nursing Database, and the associations between hypertension and OA development in knees, hips and hands were analyzed by calculating the odds ratio (OR).
Abstract: Literature examining the relationship between elevated blood pressure and osteoarthritis (OA) has yielded conflicting results. This study aimed to systematically review the relationship between hypertension and OA in both load-bearing and non-load-bearing joints.A systematic literature search was performed on Embase, Emcare, MEDLINE and Ovid Nursing Database. The associations between hypertension and OA development in knees, hips and hands were analysed by calculating the odds ratio (OR).A total of 26 studies with 97,960 participants were included. The overall odds of having OA significantly increased in the people with hypertension compared to the normotensive ones (OR = 1.60, 95%CI = 1.33, 1.94). The association of hypertension with OA was detected in knee (OR = 1.62, 95%CI = 1.32, 1.98), not in hand (OR = 1.19, 95%CI = 0.92, 1.53). Moreover, there existed a stronger association of hypertension with radiographic knee OA (OR = 1.89, 95%CI = 1.40, 2.54) than symptomatic knee OA (OR = 1.39, 95%CI = 1.17, 1.65). The association between hypertension and radiographic knee OA remained statistically significant for the studies that adjusted for body mass index (BMI) (OR = 1.42, 95%CI = 1.13, 1.78), and was particularly strong in women (OR = 2.27, 95%CI = 1.17, 4.39).A BMI-independent association between hypertension and radiographic knee OA existed with potential sex variation, which warrants further investigations into the underlying genetic, hormonal and environmental factors.The translational potential of this article: Blood pressure has been reported to link with OA for years ago, however, its contribution to OA is still unclear and conflicted in different reports. This review indicated an intimate relationship between hypertension and structural damages of knee OA, rather than simply chronic joint pain, especially in women. This finding not only provides stronger support for further investigations into the causal risk factor, i.e. hypertension, of OA from tissue level to molecular level, but also putting forward a novel thinking in OA pathogenesis and its therapy strategies.This study further strengthen the association between hypertension and radiographic knee OA. It points in a vascular aetiology hypothesis of OA. It might open up a new avenue for repositioning anti-hypertensive medications for osteoarthritis treatment.
TL;DR: In this paper, the authors investigated subchondral bone marrow lesions (BMLs) in knee OA patients who underwent total knee arthroplasty (TKA), and evaluated the associations of osteoclastogenesis and nerve growth.
Abstract: Background/objective Subchondral bone marrow lesions (BMLs) are common magnetic resonance imaging (MRI) features in joints affected by osteoarthritis (OA), however, their clinical impacts and mechanisms remain controversial. Thus, we aimed to investigate subchondral BMLs in knee OA patients who underwent total knee arthroplasty (TKA), then evaluate the associations of osteoclastogenesis and nerve growth in subchondral BMLs with clinical symptoms. Methods Total 70 patients with primary symptomatic knee OA were involved, then separated into three groups based on MRI (without BMLs group, n = 14; BMLs without cyst group, n = 37; BMLs with cyst group, n = 19). Volume of BMLs and cyst-like lesions was calculated via the OsiriX system. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was used to assess clinical symptoms. Histology and immunohistochemistry were deployed to assess subchondral osteoclastogenesis and nerve distribution. Pearson's correlation coefficient was used to evaluate the associations between volume of BMLs and joint symptoms, and to assess the associations of osteoclastogenesis and nerve growth in subchondral BMLs with joint symptoms. Results In BMLs combined with cyst group, patients exhibited increased osteoclastogenesis and nerve distribution in subchondral bone, as shown by increased expression of tartrate resistant acid phosphatase (TRAP) and protein gene product 9.5 (PGP9.5). Volume of subchondral cyst-like component was associated with joint pain (p Conclusion The subchondral cyst-like lesion was an independent factor for inducing pain in OA patients; osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for this joint pain. The translational potential of this article Our results indicated that the increased osteoclastogenesis and nerve growth in subchondral cyst-like lesions could account for the pain of OA joints. These findings may provide valuable basis for the treatment of OA.
TL;DR: In this paper , a biodegradable Mg implant was proposed to alleviate the development of osteonecrosis of the jaw via enhancing angiogenesis, which is a serious complication associated with antiresorptive and antiangiogenic medications.
Abstract: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with antiresorptive and antiangiogenic medications, of which impaired angiogenesis is a key pathological alteration. Since Magnesium (Mg)-based implants possess proangiogenic effects, we hypothesized that the biodegradable Mg implant could alleviate the development of MRONJ via enhancing angiogenesis.MRONJ model was established and divided into the Veh + Ti group (Vehicle-treated rat, with Titanium (Ti) implant), BP + Ti group (Bisphosphonate (BP)-treated rat, with Ti implant), BP + Mg group (BP-treated rat, with Mg implant), BP + Mg + SU5416 group (BP-treated rat, with Mg implant and vascular endothelial growth factor (VEGF) receptor-2 inhibitor), BP + Mg + BIBN group (BP-treated rat, with Mg implant and calcitonin gene-related peptide (CGRP) receptor antagonist), and BP + Mg + SU5416+BIBN group (BP-treated rat, with Mg implant and VEGF receptor-2 inhibitor and CGRP receptor antagonist). The occurrence of MRONJ, alveolar bone necrosis, new bone formation and vessel formation were assessed by histomorphometry, immunohistochemistry, and micro-CT analysis.Eight weeks after surgery, the BP + Mg group had significantly reduced occurrence of MRONJ-like lesion and histological osteonecrosis, increased bone microstructural parameters, and increased expressions of VEGFA and CGRP, than the BP + Ti group. By simultaneously blocking VEGF receptor-2 and CGRP receptor, the vessel volume and new bone formation in the BP + Mg group were significantly decreased, meanwhile the occurrence of MRONJ-like lesion and histological bone necrosis were significantly increased.Biodegradable Mg implant could alleviate the development of MRONJ-like lesion, possibly via upregulating VEGF- and CGRP-mediated angiogenesis. Mg-based implants have the translational potential to be developed as a novel internal fixation device for patients with the risk of MRONJ.This work reports a biodegradable Mg implant which ameliorates the development of MRONJ-like lesions possibly due to its angiogenic property. Mg-based implants have the potential to be developed as a novel internal fixation device for patients at the risk of MRONJ.
TL;DR: Wang et al. as discussed by the authors investigated the effect of Baicalein (BA) on osteosarcoma (OS) and found that BA significantly suppressed tumor growth in vitro and in vivo.
Abstract: Osteosarcoma (OS) is a common type of malignant bone tumor in adolescents with high risk of metastasis. However, the clinical management still remains unsatisfactory. Traditional Chinese medicine (TCM) has been widely considered as an alternative treatment, and their extracts have proved to possess great potential for drug discovery. Baicalein (BA), the active pharmaceutical ingredient of rhizoma coptidis, was proved to have anti-tumor properties in OS, but the mechanism remains poorly understood.The potential anti-cancer effects on cell growth, cell cycle, apoptosis and migration were examined in OS cells. Moreover, the lncRNA-Neighboring Enhancer of FOXA2 (lncRNA-NEF) and Wnt/β-catenin signaling were detected by qPCR and Western blotting assays. The in vivo effect of GA on tumor growth was investigated using a xenograft mice model.In the present study, BA was found to significantly suppress tumor growth in vitro and in vivo. And it was also found to inhibit the invasion and metastasis as well. As for the mechanism investigation, lncRNA-NEF was obviously upregulated by BA in OS cells, and thus induced the inactivation of Wnt/β-catenin signaling. Moreover, lncRNA-NEF knockdown partially reversed the BA-induced anti-cancer activities; and successfully compensated the suppressive effect on Wnt/β-catenin signaling. We therefore suggested that BA induced the inactivation of Wnt/β-catenin signaling through promoting lncRNA-NEF expression.In conclude, our results demonstrated that BA suppressed tumor growth and metastasis in vitro and in vivo through an lncRNA-NEF driven Wnt/β-catenin regulatory axis, in which lncRNA-NEF was upregulated by BA, and thus induced the inactivation of Wnt/β-catenin signaling.The findings derived from this study validates the anti-cancer activity of BA in OS and provides a novel underlying mechanism, which suggest that BA may be a potential candidate to develop the effective drug for OS patients.
TL;DR: In this paper , a mouse model induced by ovariectomy (OVX) and conducted fecal microbiota transplantation (FMT) by gavage every day for 8 weeks, and the bone mass and micro-architecture of mice were evaluated by micro computed tomography (Micro-CT).
Abstract: Osteoporosis (OP) is a systemic metabolic bone disease characterized by decreased bone mass and destruction of bone microstructure, which tends to result in enhanced bone fragility and related fractures. The postmenopausal osteoporosis (PMOP) has a relatively high proportion, and numerous studies reveal that estrogen-deficiency is related to the imbalance of gut microbiota (GM), impaired intestinal mucosal barrier function and enhanced inflammatory reactivity. However, the underlying mechanisms remain unclear and the existing interventions are also scarce.In this study, we established a mouse model induced by ovariectomy (OVX) and conducted fecal microbiota transplantation (FMT) by gavage every day for 8 weeks. Subsequently, the bone mass and microarchitecture of mice were evaluated by the micro computed tomography (Micro-CT). The intestinal permeability, pro-osteoclastogenic cytokines expression, osteogenic and osteoclastic activities were detected by the immunohistological analysis, histological examination, enzyme-linked immunosorbent assay (ELISA) and western blot analysis accordingly. Additionally, the composition and abundance of GM were assessed by 16S rRNA sequencing and the fecal short chain fatty acids (SCFAs) level was measured by metabolomics.Our results demonstrated that FMT inhibited the excessive osteoclastogenesis and prevented the OVX-induced bone loss. Specifically, compared with the OVX group, FMT enhanced the expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin) and suppressed the release of pro-osteoclastogenic cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)). Furthermore, FMT also optimized the composition and abundance of GM, and increased the fecal SCFAs level (mainly acetic acid and propionic acid).Collectively, based on GM-bone axis, FMT prevented the OVX-induced bone loss by correcting the imbalance of GM, improving the SCFAs level, optimizing the intestinal permeability and suppressing the release of pro-osteoclastogenic cytokines, which may be an alternative option to serve as a promising candidate for the prevention and treatment of PMOP in the future.This study indicates the ingenious involvement of GM-bone axis in PMOP and the role of FMT in reshaping the status of GM and ameliorating the bone loss in OVX-induced mice. FMT might serve as a promising candidate for the prevention and treatment of PMOP in the future.
TL;DR: In this paper , the role of systemic hemodynamic mechanical stress in subchondral bone remodeling and the pathogenesis of osteoarthritis was investigated from a biomechanical perspective.
Abstract: Osteoarthritis (OA) is no longer regarded as a simple wear-and-tear problem of articular cartilage. Instead, OA is a whole joint disorder involving both cartilaginous and non-cartilaginous tissues such as subchondral bone and synovium. Among them, subchondral bone undergoes constant remodeling in response to the changes of mechanical environment. Current understanding of subchondral bone disturbance in OA is limited to its link with an altered local mechanical loading as a result of ligament or meniscus injury. Very recently, hypertension, the most common vascular morbidity, has been emerged as an independent risk factor of OA. It might suggest a plausible role of systemic hemodynamic mechanical stress in subchondral bone remodeling and the pathogenesis of OA. However, their relationship remains not fully understood. Based on our preliminary clinical observation on the association of hemodynamic parameters with subchondral bone mass and microstructure in late-stage knee OA patients, we formulate a vascular etiology hypothesis of OA from a mechanobiology perspective. Noteworthily, hemodynamic stress associated with subchondral bone mineral density; yet compressive mechanical loading does not. Furthermore, hemodynamic parameters positively correlated with subchondral plate-like trabecular bone volume but negatively associated with rod-like trabecular bone volume. In contrast, compressive mechanical loading tends to increase both plate-like and rod-like trabecular bone volume. Taken together, it warrants further investigations into the distinct role of hemodynamic or compressive stress in shaping subchondral bone in the pathophysiology of OA.This work provides a new insight, from the angle of biomechanics, into the emerging role of vascular pathologies, such as hypertension, in the pathogenesis of OA. It might open up a new avenue for the development of a mechanism-based discovery of novel diagnostics and therapeutics.
TL;DR: In this article , an unsupervised consensus clustering was performed based on the most variable genes to identify osteoarthritis subclusters, which is meaningful for the development of therapies that target specific types of OA pathogenesis.
Abstract: The heterogeneity of osteoarthritis (OA) significantly limits the effectiveness of pharmacological treatments in an unselected patient population. In this context, the identification of OA subtypes is meaningful for the development of therapies that target specific types of OA pathogenesis.Expression array profiles of 70 OA and 36 control synovial samples were extracted from the GEO database. Unsupervised consensus clustering was performed based on the most variable genes to identify OA subclusters. Next, Joint samples from OA patients were obtained. We divided the OA patient into two subpopulations according to synovial ADCY7 levels. Synovium and cartilage samples from different OA subpopulations were evaluated. In addition, we established a high-fat diet (HFD)-induced rat OA model. We evaluated OA progression, lipid metabolism, synovitis and fibroblast-like synoviocytes (FLS) function in this HFD-induced OA model.70 OA patients were categorized into three distinct subclusters. We noted that one subcluster was characterized by synovial lipid metabolism disorder GO terms. We further identified the most noticeable KEGG pathway "Regulation of lipolysis in adipocytes" in this subcluster as well as the most significantly differentially expressed gene, ADCY7. We found that the ADCY7 high expressing group (32.6%) exhibited features of synovial inflammatory lipolysis epithelial-mesenchymal transition (EMT) tendency, as well as faster join space narrowing. The HFD induced OA-like degeneration in rat joints. We observed similar synovial inflammatory lipolysis and EMT in FLS, characterized by higher proliferative and invasive activity and elevated proinflammatory and procatabolic properties. ADCY7 was highly expressed in the synovium of the HFD-OA model rats and the inhibition of ADCY7 effectively attenuated these HFD-induced degenerative changes as well as synovial inflammatory lipolysis and FLS dysfunction. In HFD-FLSs, ADCY7 promoted the phosphorylation of PKA as well as its downstream lipid droplet-associated protein PLIN1 and hormone-sensitive lipase (HSL). The inhibition of PKA largely alleviated ADCY7-mediated HFD-FLS dysfunction.We described a synovial EMT and lipid metabolism disorder in the pathogenesis of OA. This novel mechanism may represent a currently undefined OA subtype. ADCY7 is a potential molecular marker of this pathomechanism.Utilizing synovial samples from OA patients, we identified a subpopulation with high ADCY7 expression. This may represent a currently undefined OA subtype and explain the clinical phenomenon of more severe synovial inflammation in obese OA patients. In addition, we established an HFD-induced OA rat model and found an upregulation of ADCY7 in the synovium. We confirmed that the inhibition of ADCY7 could effectively attenuate HFD-induced degenerative changes as well as the inflammatory lipolysis and FLS dysfunction observed in the rat model. This suggests that ADCY7 and its downstream pathways are potential pharmacological targets for treating this lipid-metabolism-disorder-related OA mechanism.
TL;DR: In this article , the accuracy and precision of one newly developed automatic PL-QCT system to measure spinal bone mineral density (BMD) and diagnose osteoporosis was validated.
Abstract: Currently dual-energy X-ray absorptiometry (DXA) and phantom-based quantitative computed tomography (PB-QCT) have been utilized to diagnose osteoporosis widely in clinical practice. While traditional phantom-less QCT (PL-QCT) is limited by the precision of manual calibration using body tissues, such as fat and muscle.The aim of this study is to validate the accuracy and precision of one newly-developed automatic PL-QCT system to measure spinal bone mineral density (BMD) and diagnose osteoporosis.A total of 36 patients were enrolled for comparison of BMD measurement between DXA and QCT. CT images of 63 patients were analyzed by both PB-QCT and newly developed automatic PL-QCT system, then the BMD results generated by the automatic PL-QCT were utilized to diagnose osteoporosis. The diagnostic outcomes were compared with that of DXA and PB-QCT to assess the performance of the new system.BMD test results showed that the automatic PL-QCT system had higher precision than previous studies performed with QCT, while maintaining similar capability to diagnose osteoporosis as DXA and PB-QCT. Area under curve (AUC) result of PL-QCT was larger than 0.8 for predicting spine DXA T-score in receiver operating characteristic (ROC) analysis. Pearson correlation analysis (r = 0.99) showed strong linear correlation and Bland-Altman analysis (bias = 3.0mg/cc) indicated little difference between the two methods. The precision result (CV = 0.89%) represented good reproducibility of the new system.The traditional PL-QCT system has relatively low reproducibility due to the manual selection of the region of interest (ROI) of body tissues. Automatic selection of ROI in this new system makes the BMD testing more convenient and improves precision significantly. Compared with traditional BMD measurement methods, the automatic PL-QCT system had higher precision in accurate diagnosis of osteoporosis with great potential in translational research and wide clinical application.With high accuracy and precision, the automatic PL-QCT system could serve as an opportunistic screening tool for osteoporosis patients in the future. It could also facilitate related researches by providing more reliable data collection, both retrospectively and longitudinally.
TL;DR: In this article , the authors explored the impact of exercise on myokine secretion in the postmenopausal osteoporosis (PMOP) process and found that exogenous kynurenine aminotransferases (Kats) treatment alleviated bone mineral loss and microstructure destruction in PMOP mice by inhibiting osteoclast maturation and increasing osteoblast viability.
Abstract: Reduced serum estrogen levels in postmenopausal patients not only aggravate bone loss but also impact myokine secretion. Emerging evidence has revealed the importance of myokines in bone metabolism, and exercise can interfere with the secretion of myokines. However, few studies have explored the impact of exercise on myokine secretion in the postmenopausal osteoporosis (PMOP) process. Ten-weeks-old C57B/L6 female mice were used for constructing the postmenopausal osteoporosis model. The expression levels of kynurenine aminotransferases (Kats) were detected by RT-PCR and Western Blot. The concentration of serum kynurenic acid (Kyna) was detected by HPLC-MS. Micro-CT analysis was used for determine the changes of bone mineral density and the microstructure. The primary osteoblast and osteoclast were isolated from mice to determine the effect and mechanism of Kyna on the bone formation and resorption. In our research, we found a lower serum level of muscle-derived kynurenic acid (Kyna) in PMOP model mice, accompanied by a decreased level of kynurenine aminotransferases (Kats) in the gastrocnemius muscle. Moreover, treadmill-running exercise upregulated the muscle levels of KATs and increased the serum concentration of Kyna, which was positively correlated with the alleviation of bone loss. Furthermore, we found that exogenous Kyna treatment alleviated bone mineral loss and microstructure destruction in PMOP mice by inhibiting osteoclast maturation and increasing osteoblast viability. Mechanistically, we observed that Kyna reduced the NFκB p65 phosphorylation level by activating the Gpr35 receptor, which inhibited NFATc1 expression in osteoclasts and upregulated Runx2 expression in osteoblasts. Our results revealed that the muscle levels of Kats and serum level of Kyna were negatively correlated with the severity of PMOP. Exercise intervention and exogenous Kyna treatment alleviated the impairment of bone microstructure through the Gpr35 receptor, paving the way for a novel therapeutic intervention in PMOP. This study provides evidences that Kyna could increase the osteoblastgenesis and inhibit the osteoclastgenesis, which could be a novel therapeutic approach for osteoporosis treatment.
TL;DR: In this paper , a review of the glucagon-like peptide-1 receptor (GLP-1R) pathway, molecular mechanisms and phenotypes related to OA pathogenesis is presented.
Abstract: Osteoarthritis (OA) is a degenerative joint disease affecting millions of people worldwide. In OA, chondrocytes, synovial cells and other joint cells become activated when exposed to an abnormal environment, including mechanical stress, inflammatory cytokines or disorganization of matrix proteins. Several analogues of the hormones called incretins have been developed and are used notably for treating type 2 diabetes mellitus. Data has accumulated to suggest that incretinomimetics, which bind to the glucagon-like peptide-1 receptor (GLP-1R), have beneficial pleiotropic effects such as immunomodulation, anti-inflammation and neuronal protection. Thus, because of their anti-inflammatory properties, GLP-1-based therapies could benefit OA patients. This review focuses on the GLP-1R pathway, molecular mechanisms and phenotypes related to OA pathogenesis.The search for new therapeutic targets to treat people suffering from OA remains urgent as there is currently no disease-modifyingtherapy available for this disease. This review discusses how GLP-1 analogues could be potential DMOADs for treating OA thanks to their anti-inflammatory, immunoregulatory and differentiation properties.
TL;DR: Clusterin (CLU) is an ATP-independent holdase chaperone that prevents proteotoxicity as a consequence of protein aggregation as discussed by the authors , which is a ∼60 kDa disulfide-linked heterodimeric protein involved in the clearance of cellular debris and the regulation of apoptosis.
Abstract: Clusterin (CLU; also known as apolipoprotein J) is an ATP-independent holdase chaperone that prevents proteotoxicity as a consequence of protein aggregation. It is a ∼60 kDa disulfide-linked heterodimeric protein involved in the clearance of cellular debris and the regulation of apoptosis. CLU has been proposed to protect cells from cytolysis by complement components and has been implicated in Alzheimer's disease due to its ability to bind amyloid-β peptides and prevent aggregate formation in the brain. Recent studies suggest that CLU performs moonlighting functions. CLU exists in two major forms: an intracellular form and a secreted extracellular form. The intracellular form of CLU may suppress stress-induced apoptosis by forming complexes with misfolded proteins and facilitates their degradation. The secreted form of CLU functions as an extracellular chaperone that prevents protein aggregation.In this review, we discuss the published literature on the biology of CLU in cartilage, chondrocytes, and other synovial joint tissues. We also review clinical studies that have examined the potential for using this protein as a biomarker in synovial and systemic fluids of patients with rheumatoid arthritis (RA) or osteoarthritis (OA).Since CLU functions as an extracellular chaperone, we propose that it may be involved in cytoprotective functions in osteoarticular tissues. The secreted form of CLU can be measured in synovial and systemic fluids and may have translational potential as a biomarker of early repair responses in OA.There is significant potential for investigating synovial and systemic CLU as biomarkers of OA. Future translational and clinical orthopaedic studies should carefully consider the diverse roles of this protein and its involvement in other comorbidities. Therefore, future biomarker studies should not correlate circulating CLU levels exclusively to the process of OA pathogenesis and progression. Special attention should be paid to CLU levels in synovial fluid.There is significant potential for investigating synovial and systemic CLU as a predictive biomarker of osteoarthritis (OA) progression and response to novel treatments and interventions. Given that CLU plays diverse roles in other comorbidities such as rheumatoid arthritis (RA) and obesity, future translational and clinical orthopaedic biomarker studies should not directly correlate circulating CLU levels to the process of OA pathogenesis and progression. However, special attention should be paid to CLU levels in synovial fluid. The cytoprotective properties of CLU may support the implementation of regenerative strategies and new approaches for developing targeted therapeutics for OA.
TL;DR: Wang et al. as discussed by the authors constructed a porous polyetheretherketone (PEEK) scaffold via 3D printing, surface-engineered with concentrated sulfuric acid for 15 s, 30 s, and 60 s, respectively.
Abstract: The treatment of cartilage lesions has always been a difficult problem. Although cartilage tissue engineering provides alternative treatment options for cartilage lesions, biodegradable tissue engineering scaffolds have limitations.In this study, we constructed a porous PEEK scaffold via 3D printing, surface-engineered with concentrated sulfuric acid for 15 s (SPK-15), 30 s (SPK-30), and 60 s (SPK-60). We systematically evaluated the physical and chemical characteristics and biofunctionalities of the scaffolds, and then evaluated the macrophage polarization modulating ability and anti-inflammatory effects of the sulfonated PEEK, and observed the cartilage-protective effect of SPK using a co-culture study. We further evaluated the repair effect of PEEK and SPK by implanting the prosthetic scaffold into a cartilage defect in a rabbit model.Compared to the PEEK, SPK-15 and SPK-60 scaffolds, SPK-30 has a good micro/nanostructure, appropriate biomechanical properties (compressive modulus, 43 ± 5 MPa; Shaw hardness, 20.6 ± 1.3 HD; close to native cartilage, 30 ± 8 MPa, 17.8 ± 0.8 HD), and superior biofunctionalities. Compared to PEEK, sulfonated PEEK can favor macrophage polarization to the M2 phenotype, which increases anti-inflammatory cytokine secretion. Furthermore, SPK can also prevent macrophage-induced cartilage degeneration. The in-vivo animal experiment demonstrates that SPK can favor new tissue ingrowth and integration, prevent peri-scaffold cartilage degeneration and patellar cartilage degeneration, inhibit inflammatory cytokine secretion, and promote cartilage function restoration.The present study confirmed that the 3D printed porous sulfonated PEEK scaffold could promote cartilage functional repair, and suggests a new promising strategy for treating cartilage defects with a functional prosthesis that spontaneously inhibits nearby cartilage degeneration.In the present study, we propose a new cartilage repair strategy based on a porous, non-biodegradable polyetheretherketone (PEEK) scaffold, which may bring up a new treatment route for elderly patients with cartilage lesions in the future.
TL;DR: Based on the imaging features of ONFH, different classification systems have been developed to evaluate the severity and prognosis of the disease, which is pivotal for implementation of treatment strategy, especially the joint-preserving surgery as mentioned in this paper .
Abstract: Osteonecrosis of the femoral head (ONFH) is a recalcitrant ischemic disorder, which could be classified into two major categories: traumatic and nontraumatic. Regardless of different risk factors, it has been testified that ONFH results from primitive vascular problems, leading to temporary or permanent loss of blood supply to bone tissue. Histopathological and microarchitectural alterations ensues, which is a gradual evolutionary process involving bone marrow and osteocyte necrosis, progressive destruction of subchondral bone, unsuccessful reparative process, and eventual articular collapse and degenerative arthritis. Based on the imaging features of ONFH, different classification systems have been developed to evaluate the severity and prognosis of the disease, which is pivotal for implementation of treatment strategy, especially the joint-preserving surgery. However, patients classified with the same severity stage, especially in the peri-collapse stage, sometimes responded differently after similar joint-preserving surgery. The unusual phenomenon may be attributed to the limitation of the current imaging classification systems, which might underestimate the disease severity, especially when referring to the early stages. In this review, we briefly summarize the etiology and pathogenesis of ONFH. The imaging features and staging classification systems of ONFH are also described. More importantly, we focus on histopathological and microstructural alterations of the femoral head, and provide an overview of their essential contribution to ONFH progression. Given the observation of discordance between imaging characteristics and histopathological alterations, a substantial amount of research on the relationship between imaging and histopathological features is required to further modify and revise the current wide-accepted classification systems.
TL;DR: Wang et al. as mentioned in this paper investigated whether Synovium-derived stromal cells (SDSCs) could help chondrocytes to maintain chondrogenic phenotype and suppress hypertrophic differentiation in cartilage repairs.
Abstract: Costal chondrocytes (CCs), as a promising donor cell source for cell-based therapy for cartilage repair, have strong tendency of hypertrophy and calcification, which limited CCs from further application in cartilage regenerative medicine. Synovium-derived stromal cells (SDSCs), have shown their beneficial effect for chondrocytes to maintain phenotype. This study aims to investigate whether SDSCs could help CCs to maintain chondrogenic phenotype and suppress hypertrophic differentiation in cartilage repairs.CCs were directly cocultured with SDSCs in pellet or indirectly cocultured using a conditioned medium in vitro for 3 weeks. Cartilage matrix formation and hypertrophic differentiation of CCs were analyzed by RT-PCR, biochemical assays, and histological staining. Cocultured pellets were implanted into the osteochondral defects made on the femoral groove of the rats. Then, macroscopic and histological evaluations were performed.Pellets formed by CCs alone and CCs cocultured with SDSCs reveal equal cartilage matrix deposition. However, the gene expression of type X collagen was significantly downregulated in cocultured pellets. Immunohistochemistry analysis revealed suppressed expression of type X collagen in cocultured pellets, indicating SDSCs may suppress hypertrophic differentiation of chondrocytes. Further in indirect coculture experiment, SDSCs suppressed type X collagen expression as well and promoted the proliferation of CCs, indicating SDSCs may influence CCs by paracrine mechanism. The pellets implanted in the osteochondral defects showed good restoration effects, whereas the grafts constructed with CCs and SDSCs showed lower type X expression levels.These results suggest that SDSCs may maintain the phenotype of CCs and prevent the hypertrophic differentiation of CCs in cartilage repair.The Translational Potential of this Article: CCs is a promising donor cell source for cell-based therapy for cartilage repair. Based on our study, cocultured with SDSCs weakened the tendency of hypertrophy and calcification of CCs, which provide a potential usage of SDSCs in CCs-based cartilage repair therapy to suppress newly formed cartilage calcification and improve clinical outcomes.