Showing papers in "Cartilage in 2011"
TL;DR: 1-step surgery with BMAC and collagen I/III matrix could be a viable technique in the treatment of grade IV knee chondral lesions and showed significant improvement in all scores at final follow-up.
Abstract: Objective:The purpose of our study was to determine the effectiveness of cartilage repair utilizing 1-step surgery with bone marrow aspirate concentrate (BMAC) and a collagen I/III matrix (Chondro-...
200 citations
TL;DR: In this paper, the authors proposed guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies, which could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies.
Abstract: Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character.
142 citations
TL;DR: Autologous osteochondrals transplantation is a reproducible and primary treatment strategy for large osteochondral lesions of the talus for large bone marrow aspirate concentrate patients.
Abstract: Objective:To present the functional results after autologous osteochondral transplantation with bone marrow aspirate concentrate in 72 patients, while placing an emphasis on the surgical technique....
136 citations
TL;DR: In this paper, the authors used a reductionist approach using acute and chronic chondral defects in immature laboratory species, particularly the rabbit, was considered adequate; however, if successful and timely translation from animal models to regulatory approval and clinical use is the goal, a stepwise development using laboratory animals for screening and early development work followed by larger species such as the goat, sheep and horse for late development and pivotal studies is recommended.
Abstract: Investigational devices for articular cartilage repair or replacement are considered to be significant risk devices by regulatory bodies. Therefore animal models are needed to provide proof of efficacy and safety prior to clinical testing. The financial commitment and regulatory steps needed to bring a new technology to clinical use can be major obstacles, so the implementation of highly predictive animal models is a pressing issue. Until recently, a reductionist approach using acute chondral defects in immature laboratory species, particularly the rabbit, was considered adequate; however, if successful and timely translation from animal models to regulatory approval and clinical use is the goal, a step-wise development using laboratory animals for screening and early development work followed by larger species such as the goat, sheep and horse for late development and pivotal studies is recommended. Such animals must have fully organized and mature cartilage. Both acute and chronic chondral defects can be used but the later are more like the lesions found in patients and may be more predictive. Quantitative and qualitative outcome measures such as macroscopic appearance, histology, biochemistry, functional imaging, and biomechanical testing of cartilage, provide reliable data to support investment decisions and subsequent applications to regulatory bodies for clinical trials. No one model or species can be considered ideal for pivotal studies, but the larger animal species are recommended for pivotal studies. Larger species such as the horse, goat and pig also allow arthroscopic delivery, and press-fit or sutured implant fixation in thick cartilage as well as second look arthroscopies and biopsy procedures.
120 citations
TL;DR: Two knee-specific instruments, titled the International Knee Documentation Committee Subjective Knee Form and the Knee injury and Osteoarthritis and Outcome Score, both fulfill the basic requirements for reliability, validity, and responsiveness in cartilage repair patients.
Abstract: Objective:The purpose of this article is to describe and recommend patient-reported outcome instruments for use in patients with articular cartilage lesions undergoing cartilage repair interventions.Methods:Nonsystematic literature search identifying measures addressing pain and function evaluated for validity and psychometric properties in patients with articular cartilage lesions.Results:The knee-specific instruments, titled the International Knee Documentation Committee Subjective Knee Form and the Knee injury and Osteoarthritis and Outcome Score, both fulfill the basic requirements for reliability, validity, and responsiveness in cartilage repair patients. A major difference between them is that the former results in a single score and the latter results in 5 subscores. A single score is preferred for simplicity’s sake, whereas subscores allow for evaluation of separate constructs at all levels according to the International Classification of Functioning.Conclusions:Because there is no obvious superio...
112 citations
TL;DR: Equine chondral defect models that have been recently recognized to have specific advantages for translation into human articular cartilage regeneration are reviewed.
Abstract: Articular cartilage injuries of the knee and ankle are common, and a number of different methods have been developed in an attempt to improve their repair. Clinically, there are 2 distinct aims of cartilage repair: 1) restoration of joint function and 2) prevention or at least delay of the onset of osteoarthritis. These goals can potentially be achieved through replacement of damaged or lost articular cartilage with tissue capable of functioning under normal physiological environments for an extended period, but limitations of the final repair product have long been recognized and still exist today. Screening of potential procedures for human clinical use is done by preclinical studies using animal models. This article reviews equine chondral defect models that have been recently recognized to have specific advantages for translation into human articular cartilage regeneration. Defect models in the femoropatellar, femorotibial, and tibiotalar joints have been developed. The horse provides the closest approximation to humans in terms of articular cartilage and subchondral bone thickness, and it is possible to selectively leave the entire calcified cartilage layer or completely remove it. The defect on the equine medial femoral condyle emulates medial femoral condylar lesions in humans. Other advantages of the equine model include an ability to use an arthroscope to create lesions and perform second-look arthroscopies, the large lesion size allowing for more tissue for evaluation, and the ability to have controlled exercise and test the ability of the repair to cope with athletic exercise as well as institute rehabilitation regimens.
107 citations
TL;DR: Clinical outcome data of 4 patients who have reached the 24-month postimplantation milestone indicate early positive outcomes and suggest that this technique is capable of improving clinical symptoms and MRI data suggest that defect filling is possible and persists to at least 2 years.
Abstract: Objective:This case study of 4 patients followed for at least 2 years was conducted to evaluate a cartilage repair procedure that involves transplanting particulated juvenile allograft cartilage.Design:A multicenter, prospective, single-arm, 25-subject case study was designed to evaluate clinical outcomes such as IKDC and KOOS scores as well as the extent and quality of repair with MRI. In addition, there is an option for the transplants to be biopsied at various time points after implantation (up to 5 years). Currently, 25 patients with 1 or 2 chondral lesions on the femoral condyles and trochlea have been enrolled and treated in the prospective study.Results:The first 4 patients have completed an evaluation at 24 months postoperative follow-up. Improvements in clinical outcomes over the preoperative baseline data have been observed.Conclusions:The present report describes, for the first time, clinical intermediate-term results of a novel cartilage repair procedure that involves transplanting particulate...
99 citations
TL;DR: The size of cartilage defects measured by preoperative MRI with surgical measurements after debridement was compared, and on average the final total defect area per knee was 65% larger than estimated preoperatively by MRI.
Abstract: Objective:Anecdotal evidence suggests that MRI frequently underestimates the size of cartilage defects when compared with final lesion size after debridement of all degenerated tissue. This has pot...
68 citations
TL;DR: An overview of the current state of the art of MRI of Cartilage repair is provided with a focus on morphological depiction of cartilage and the use of functional (biochemical) MR methodologies for the visualization of the ultrastructure ofcartilage repair.
Abstract: Articular cartilage lesions are a common pathology of the knee joint, and many patients may benefit from cartilage repair surgeries that offer the chance to avoid the development of osteoarthritis or delay its progression. Cartilage repair surgery, no matter the technique, requires a noninvasive, standardized, and high-quality longitudinal method to assess the structure of the repair tissue. This goal is best fulfilled by magnetic resonance imaging (MRI). The present article provides an overview of the current state of the art of MRI of cartilage repair. In the first 2 sections, preclinical and clinical MRI of cartilage repair tissue are described with a focus on morphological depiction of cartilage and the use of functional (biochemical) MR methodologies for the visualization of the ultrastructure of cartilage repair. In the third section, a short overview is provided on the regulatory issues of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) regarding MR follow-up studies of patients after cartilage repair surgeries.
67 citations
TL;DR: Detailed methodological recommendations were developed for the statistical study design, patient recruitment, control group considerations, study endpoint definition, documentation of results, and inclusion and exclusion criteria for the design and conduct of scientifically sound cartilage repair study protocols.
Abstract: Objective:To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products.Design:A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for the design, reporting, and interpretation of studies in this field.Results:Current literature reflects the methodological limitations of the scientific evidence available for articular cartilage repair. However, clinical trial databases of ongoing trials document a trend suggesting improved study designs and clinical evaluation methodology. Based on the current scientific information and standards of clinical care, detailed methodological recommendations were developed for the statistical study design, patient recruitment...
63 citations
TL;DR: A histological grading scheme that comprehensively and quantitatively assesses changes in multiple tissues that are associated with OA of the stifle joint in mice is developed and provides comprehensive information regarding a specific site in theStifle joint.
Abstract: Objective:Accurate histological assessment of osteoarthritis (OA) is critical in studies evaluating the effects of interventions on disease severity. The purpose of the present study was to develop...
TL;DR: The potential benefits of using gene therapy approaches for the repair of articular cartilage and meniscal fibrocartilage, including articularcartilage defects resulting from acute trauma, osteochondritis dissecans, osteonecrosis, and osteoarthritis are focused on.
Abstract: The concept of using gene transfer strategies for cartilage repair originates from the idea of transferring genes encoding therapeutic factors into the repair tissue, resulting in a temporarily and spatially defined delivery of therapeutic molecules to sites of cartilage damage. This review focuses on the potential benefits of using gene therapy approaches for the repair of articular cartilage and meniscal fibrocartilage, including articular cartilage defects resulting from acute trauma, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Possible applications for meniscal repair comprise meniscal lesions, meniscal sutures, and meniscal transplantation. Recent studies in both small and large animal models have demonstrated the applicability of gene-based approaches for cartilage repair. Chondrogenic pathways were stimulated in the repair tissue and in osteoarthritic cartilage using genes for polypeptide growth factors and transcription factors. Although encouraging data have been generated, a successful translation of gene therapy for cartilage repair will require an ongoing combined effort of orthopedic surgeons and of basic scientists.
TL;DR: A mechanical load appears to modify cartilage degradation by IL-1 at the cellular level by reducing mRNA.
Abstract: Objective:Exposure of articular cartilage to interleukin-1 (IL-1) results in increased synthesis of matrix degrading enzymes. Previously mechanical load applied together with IL-1 stimulation was found to reduce aggrecan cleavage by ADAMTS-4 and 5 and MMP-1, -3, -9, and -13 and reduce proteoglycan loss from the extracellular matrix. To further delineate the inhibition mechanism the gene expression of ADAMTS-4 and 5; MMP-1, -3, -9, and -13; and TIMP-1, -2, and -3 were measured.Design:Mature bovine articular cartilage was stimulated with a 0.5 MPa compressive stress and 10 ng/ml of IL-1α for 3 days and then allowed to recover without stimulation for 1 additional day. The media was assayed for proteoglycan content on a daily basis, while chondrocyte gene expression (mRNA) was measured during stimulation and 1 day of recovery.Results:Mechanical load alone did not change the gene expression for ADAMTS, MMP, or TIMP. IL-1 caused an increase in gene expression for all enzymes after 1 day of stimulation while not...
TL;DR: The IAUS method provided a novel arthroscopic method for quantitative imaging of articular cartilage lesions, which provided quantitative information about the cartilage integrity and thickness, which are not available in conventional ar Throscopic surgery.
Abstract: Objective:We tested whether an intra-articular ultrasound (IAUS) method could be used to evaluate cartilage status arthroscopically in human knee joints in vivo.Design:Seven patients undergoing art...
TL;DR: Chitosan-GP/blood implant amplified the acute influx of subchondral osteoclasts through indirect mechanisms, leading to significantly improved repair and cartilage-bone integration without inducing net bone resorption.
Abstract: Objective:Cartilage-bone integration is an important functional end point of cartilage repair therapy, but little is known about how to promote integration. We tested the hypothesis that chitosan-s...
TL;DR: The purpose of this review is to describe the workup and discuss the management techniques for cartilage injuries within the adult knee.
Abstract: Cartilage injuries are frequently recognized as a source of significant morbidity and pain in patients with previous knee injuries. The majority of patients who undergo routine knee arthroscopy have evidence of a chondral defect. These injuries represent a continuum of pathology from small, asymptomatic lesions to large, disabling defects affecting a major portion of one or more compartments within the knee joint. In comparison to patients with osteoarthritis, individuals with isolated chondral surface damage are often younger, significantly more active, and usually less willing to accept limitations in activities that require higher impact. At the present time, a variety of surgical procedures exist, each with their unique indications. This heterogeneity of treatment options frequently leads to uncertainty regarding which techniques, if any, are most appropriate for patients. The purpose of this review is to describe the workup and discuss the management techniques for cartilage injuries within the adult knee.
TL;DR: The accelerated WB approach was not detrimental to graft development at any stage throughout the postoperative assessment timeline from baseline to 24 months postsurgery and may potentially accelerate patient return to normal function, while reducing postoperative muscle loss, intra-articular adhesions, and associated gait abnormalities.
Abstract: Objective: To assess the safety and efficacy of accelerated compared with traditional postoperative weightbearing (WB) rehabilitation following matrix-induced autologous chondrocyte implantation (MACI) of the knee, using MRI. Methods: A randomized controlled study design was used to assess MRI-based outcomes of MACI grafts in 70 patients (45 men, 25 women) who underwent MACI to the medial or lateral femoral condyle, in combination with either traditional or accelerated approaches to postoperative WB rehabilitation. High-resolution MRI was undertaken and assessed 8 previously defined pertinent parameters of graft repair, as well as a combined MRI composite score at 3, 12, and 24 months postsurgery. The association between clinical and MRI-based outcomes, patient demographics, chondral defect parameters, and injury/ surgery history was investigated. Results: Both groups significantly improved (P 0.05) observed between the 2 groups. Patient age, body mass index, chondral defect size, and duration of preoperative symptoms were significantly correlated (P 0.05) observed between clinical and MRI-based outcomes. Conclusion: The accelerated WB approach was not detrimental to graft development at any stage throughout the postoperative assessment timeline from baseline to 24 months postsurgery and may potentially accelerate patient return to normal function, while reducing postoperative muscle loss, intra-articular adhesions, and associated gait abnormalities.
TL;DR: MFX in the ankle can provide repair tissue (RT) quality after MFX with T2 properties similar to adjacent cartilage, and this study demonstrated significant improvement at the time of the MR examination.
Abstract: Background:Microfracture (MFX) is frequently used to treat deep cartilage defects in the ankle; however, the data on repair tissue (RT) quality after MFX are very limited at this time. T2-mapping a...
TL;DR: The clinical outcome after autologous chondrocyte transplantation and MACT in the ankle can provide good and excellent long-term outcome and resulted in repair tissue with T2 properties similar to native cartilage in the majority of cases.
Abstract: Background:New matrix-associated autologous chondrocyte transplantation (MACT) techniques may facilitate the treatment of chondral defects in talar cartilage and provide good clinical outcome in the long term. The aim of this prospective case series was to monitor the clinical outcome after autologous chondrocyte transplantation (ACT) and MACT in the ankle to gain data on the mid-term efficacy of the procedure.Methods:Seventeen cases of talar cartilage defects were assessed with the American Orthopaedic Foot and Ankle Score (AOFAS), a modified Cincinnati score, and a subjective ankle-hindfoot score (AHS) at a mean of 61 (24-135) months after surgery. Nine patients consented to an additional magnetic resonance imaging (MRI) exam, including T2 mapping at 3T. ACT was carried out with a periosteal flap (4 cases) or with a matrix-assisted ACT technique (Hyalograft C; 13 cases).Results:Significant improvement was found in all cases. The AOFAS improved from 50.0 to 87.3, the AHS from 43.8 to 84.1, and the modifi...
TL;DR: This study prospectively assesses osseous integration and early clinical results following fresh OCA with single or multiple cylindrical grafts to the femoral condyle in a cohort that showed significant improvements after 2 years of treatment with OCA.
Abstract: Objective:Fresh osteochondral allograft transplantation (OCA) is an increasingly available option for patients with damage to the bone-cartilage complex of the distal femur. This study prospectivel...
TL;DR: DN gel strength and toughness properties stem from optimized entanglement of the 2 network components, and their surgical handling properties make them ideal candidates for clinical use.
Abstract: Background:In focal repair of joint cartilage and meniscus, initial stiffness and strength of repairs are generally much less than surrounding tissue. This increases early failure potential. Secure...
TL;DR: A scaffold-less, self-aggregating bioreactor model without foreign material or scaffold in which chondrocytes form a cartilage tissue analog with many features similar to native cartilage is described.
Abstract: Objective:Many approaches are being taken to generate cartilage replacement materials. The goal of this study was to use a self-aggregating suspension culture model of chondrocytes with mechanical ...
TL;DR: This study shows that Durolane™ has a half-life of 32 days in the rabbit knee joint, which is much longer compared to literature data on hyaluronic acid and other modified hyaluonic acid products.
Abstract: Objective:The aim of the present study was to investigate the intra-articular duration of Durolane™ in a rabbit model to allow comparison between Durolane™ residence time and data reported for other hyaluronic acid products as well as native hyaluronic acid.Design:14C-labeled Durolane™ was manufactured by labeling the cross-linker used for stabilization. A single injection of approximately 0.3 mL 14C-labeled Durolane™ was administered intra-articularly in both knee joints of male New Zealand White rabbits. At days 1, 2, 3, 7, 28, 60, 96, and 120 after injection, the knee joints of 4 animals were collected, and the radioactivity of the remaining gel was measured. The obtained data were fitted by exponential models to calculate the half-life of the gel. Two additional rabbits were used for histology of the joint 127 days after the injection.Results:The elimination of 14C-labeled Durolane™ followed first-order kinetics with an apparent half-life of approximately 32 days. Histology showed no morphological cha...
TL;DR: Results demonstrated the potential of cartilage smoothness markers for diagnosis of moderate radiographic OA and correlations between smoothness and pain values and smoothness loss and cartilage loss supported a link to progression of OA.
Abstract: Objective:We investigated whether surface smoothness of articular cartilage in the medial tibiofemoral compartment quantified from magnetic resonance imaging (MRI) could be appropriate as a diagnostic marker of osteoarthritis (OA).Method:At baseline, 159 community-based subjects aged 21 to 81 with normal or OA-affected knees were recruited to provide a broad range of OA states. Smoothness was quantified using an automatic framework from low-field MRI in the tibial, femoral, and femoral subcompartments. Diagnostic ability of smoothness was evaluated by comparison with conventional OA markers, specifically cartilage volume from MRI, joint space width (JSW) from radiographs, and pain scores.Results:A total of 140 subjects concluded the 21-month study. Cartilage smoothness provided diagnostic ability in all compartments (P < 0.0001). The diagnostic smoothness markers performed at least similar to JSW and were superior to volume markers (e.g., the AUC for femoral smoothness of 0.80 was higher than the 0.57 for...
TL;DR: It is proposed that an explant whole-tissue model for investigating cell-cell interactions is established, reflecting parts of the processes in the pathogenesis of joint degenerative diseases.
Abstract: Objective:The pathophysiology of osteoarthritis involves the whole joint and is characterized by cartilage degradation and altered subchondral bone turnover. At present, there is a need for biological models that allow investigation of the interactions between the key cellular players in bone/cartilage: osteoblasts, osteoclasts, and chondrocytes.Methods:Femoral heads from 3-, 6-, 9-, and 12-week-old female mice were isolated and cultured for 10 days in serum-free media in the absence or presence of IGF-I (100 nM) (anabolic stimulation) or OSM (10 ng/mL) + TNF-α (20 ng/mL) (catabolic stimulation). Histology on femoral heads before and after culture was performed, and the growth plate size was examined to evaluate the effects on cell metabolism. The conditioned medium was examined for biochemical markers of bone and cartilage degradation/formation.Results:Each age group represented a unique system regarding the interest of bone or cartilage metabolism. Stimulation over 10 days with OSM + TNF-α resulted in d...
TL;DR: Although bone marrow–derived mesenchymal cells, when supplemented with the appropriate chondrogenic factors, are a suitable source for autologous cartilage implantation, adult chondroprogenitor cells, particularly those from moderately affected regions of the osteoarthritic joints, demonstrate superior chondrogensic potential.
Abstract: Objective:The multipotential nature of stem or progenitor cells apparently makes them the ideal choice for any cell therapy, but this as yet remains to be proven. This study (30 subjects) was designed to compare the potential to repair articular cartilage of chondrocytes taken from different regions in osteoarthritic cartilage with that of mesenchymal stem cells prepared from bone marrow of the same subject.Design:Cartilage biopsies, bone marrow, and blood samples were taken from each of 30 individuals with chronic osteoarthritis (aged 62-85 years) undergoing total knee replacement. The chondrogenic potential of chondrocytes isolated from cartilage biopsies taken from different regions of osteoarthritic cartilage was compared with that of mesenchymal cells by quantitative analysis of several chondrocyte specific markers and an ex vivo cartilage differentiation assay.Results:Cartilage-derived articular chondrocytes are superior to bone marrow–derived cells when compared for their ex vivo chondrogenic poten...
TL;DR: This review summarizes the functions of c-Maf in chondrocyte differentiation and discusses the possible role of bZIP transcription factor superfamily member c- Maf in osteoarthritis progression.
Abstract: Chondrocyte differentiation in the growth plate is an important process for the longitudinal growth of endochondral bones. Sox9 and Runx2 are the most often-studied transcriptional regulators of the chondrocyte differentiation process, but the importance of additional factors is also becoming apparent. Mafs are a subfamily of the basic ZIP (bZIP) transcription factor superfamily, which act as key regulators of tissue-specific gene expression and terminal differentiation in many tissues. There is increasing evidence that c-Maf and its splicing variant Lc-Maf play a role in chondrocyte differentiation in a temporal-spatial manner. This review summarizes the functions of c-Maf in chondrocyte differentiation and discusses the possible role of c-Maf in osteoarthritis progression.
TL;DR: Comparisons of secretion products derived from human articular chondrocytes established in either long-term monolayer cultures or in scaffold-free 3-dimensional cultures show that some classic dedifferentiation and redifferentiation markers are differentially expressed in 2-D or 3-D culture configurations.
Abstract: Objective:The main goal of this study was to compare the secretion products derived from human articular chondrocytes established in either long-term monolayer cultures or in scaffold-free 3-dimensional (3-D) cultures.Methods:Stable isotope labeling of amino acids in cell culture (SILAC) was applied to investigate quantitatively the differences between proteins secreted from dedifferentiated and redifferentiated chondrocytes. Proteins in cell supernatants were resolved by 1-D gel electrophoresis and analyzed by mass spectrometry. The results from the proteomic analyses were validated by immunoblotting. Additionally, antibody arrays were used to screen culture supernatants for 79 different morphogens.Results:Quantitative SILAC showed that some relevant growth factors such as CTGF or GAS6 were elevated in monolayers, along with proteins characteristic of a dedifferentiated phenotype such as collagen type I and tenascin. In spheroids, data showed overexpression of some cartilage-specific proteins such as agg...
TL;DR: A simple, reliable method to measure the height of a condylar lesion with the lesion’s arc with the confidence interval narrower when using the goniometer is proposed.
Abstract: Purpose:To present a new method of arthroscopic measurement of the surface and location of condylar lesions.Methods:We propose measuring the height of the condylar lesion by using the lesion’s arc ...
TL;DR: This study supports the hypothesis that a difference in chondroitin sulfate disaccharides is detectable in affected newborn lambs prior to the development of lesions, and is crucial to normal cartilage formation and consequently to endochondral ossification.
Abstract: Objective:Chondroitin sulfate is the major sulfated polysaccharide attached to the core protein, aggrecan, in the hyaline cartilage matrix. Sulfation of the cartilage matrix polysaccharide is vital for normal matrix integrity and compressive stiffness of the tissue and is therefore crucial to normal cartilage formation and consequently to endochondral ossification. Several forms of chondrodysplasia, a condition resulting in clear macroscopic deficiencies in the mechanical properties of the cartilage and characterized by reduced levels of sulfate, have been identified in both human beings and animals.Design:In this study, the authors used capillary electrophoresis to investigate the sulfation state of extracted chondroitin sulfate polymers.Results:Significantly, cartilage from affected sheep had a lower ratio of the chondroitin-derived enzymatically liberated disaccharides Δdi-mono4S to Δdi-mono6S, demonstrating reduced levels of chondroitin 4-sulfate, but not chondroitin 6-sulfate, in chondrodysplastic sh...