The Roles of Mechanical Stresses in the Pathogenesis of Osteoarthritis: Implications for Treatment of Joint Injuries.
TL;DR: Advances in understanding of how altering mechanical stresses can lead to remodeling of osteoarthritic joints and how excessive stress causes loss of articular cartilage provide the basis for new biologic and mechanical approaches to the prevention and treatment of OA.
Abstract: Excessive joint surface loadings, either single (acute impact event) or repetitive (cumulative contact stress), can cause the clinical syndrome of osteoarthritis (OA). Despite advances in treatment of injured joints, the risk of OA following joint injuries has not decreased in the past 50 years. Cumulative excessive articular surface contact stress that leads to OA results from posttraumatic joint incongruity and instability, and joint dysplasia, but may also cause OA in patients without known joint abnormalities. In vitro investigations show that excessive articular cartilage loading triggers release of reactive oxygen species (ROS) from mitochondria, and that these ROS cause chondrocyte death and matrix degradation. Preventing release of ROS or inhibiting their effects preserves chondrocytes and their matrix. Fibronectin fragments released from articular cartilage subjected to excessive loads also stimulate matrix degradation; inhibition of molecular pathways initiated by these fragments prevents this e...
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18 Dec 2015
TL;DR: The progress in cell based therapies that utilize Mesenchymal Stem Cell (MSC) infusion for cartilage repair may lead to new therapeutics in the long term, however, many questions are unanswered such as the efficacy of MSCs usage in therapy.
Abstract: Articular cartilage (AC) covers the diarthrodial joints and is responsible for the mechanical distribution of loads across the joints. The majority of its structure and function is controlled by chondrocytes that regulate Extracellular Matrix (ECM) turnover and maintain tissue homeostasis. Imbalance in their function leads to degenerative diseases like Osteoarthritis (OA). OA is characterized by cartilage degradation, osteophyte formation and stiffening of joints. Cartilage degeneration is a consequence of chondrocyte hypertrophy along with the expression of proteolytic enzymes. Matrix Metalloproteinases (MMPs) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) are an example of these enzymes that degrade the ECM. Signaling cascades involved in limb patterning and cartilage repair play a role in OA progression. However, the regulation of these remains to be elucidated. Further the role of stem cells and mature chondrocytes in OA progression is unclear. The progress in cell based therapies that utilize Mesenchymal Stem Cell (MSC) infusion for cartilage repair may lead to new therapeutics in the long term. However, many questions are unanswered such as the efficacy of MSCs usage in therapy. This review focuses on the role of chondrocytes in cartilage formation and the progression of OA. Moreover, it summarizes possible alternative therapeutic approaches using MSC infusion for cartilage restoration.
294 citations
TL;DR: By reading, you can know the knowledge and things more, not only about what you get from people to people, but also about how to be successful in everything.
Abstract: By reading, you can know the knowledge and things more, not only about what you get from people to people. Book will be more trusted. As this articular cartilage and osteoarthritis, it will really give you the good idea to be successful. It is not only for you to be success in certain life you can be successful in everything. The success can be started by knowing the basic knowledge and do actions.
287 citations
TL;DR: Patients treated with ACLR have a significantly lower risk of secondary meniscal tears, symptomatic arthritis, and TKA when compared with patients treated nonoperatively after ACL tears, and early ACLR significantly reduces the risk of subsequent meniscal Tears and arthritis compared with delayed ACLR.
Abstract: Background:Reconstruction of anterior cruciate ligament (ACL) tears may potentially prevent the development of secondary meniscal injuries and arthritis.Purpose/Hypothesis:The purpose of this study was to (1) evaluate the protective benefit of ACL reconstruction (ACLR) in preventing subsequent meniscal tears or arthritis, (2) determine if earlier ACLR (<1 year after injury) offers greater protective benefits than delayed reconstruction (≥1 year after injury), and (3) evaluate factors predictive of long-term sequelae after ACLR. The hypothesis was that the incidence of secondary meniscal tears, arthritis, and total knee arthroplasty (TKA) would be higher in patients treated nonoperatively after ACL tears than patients treated with surgical reconstruction.Study Design:Cohort study; Level of evidence, 3.Methods:This retrospective study included a population-based incidence cohort of 964 patients with new-onset, isolated ACL tears between 1990 and 2000 as well as an age- and sex-matched cohort of 964 patients...
112 citations
TL;DR: The involvement of alarmins in chronic inflammatory arthritides is suggested by their presence in serum at high levels in these conditions, and their expression within inflamed synovia and synovial fluid.
Abstract: Alarmins (also known as danger signals) are endogenous molecules that are released to the extracellular milieu after infection or tissue damage. Extracellular alarmins interact with specific receptors expressed by cells that are engaged in host defence to stimulate signalling pathways that result in initiation of innate and adaptive immune responses, triggering inflammation or tissue repair. Alarmins are considered to be markers of destructive processes that occur in degenerative joint diseases (primarily osteoarthritis (OA)) and chronic inflammatory joint diseases (such as rheumatoid arthritis, psoriatic arthritis and spondylarthropathy). In OA, high mobility group protein B1 (HMGB1) and S100 proteins, along with many other alarmins, are abundantly secreted by joint cells, promoting cartilage matrix catabolism, osteophyte formation, angiogenesis and hypertrophic differentiation. The involvement of alarmins in chronic inflammatory arthritides is suggested by their presence in serum at high levels in these conditions, and their expression within inflamed synovia and synovial fluid. S100 proteins, HMGB1, IL-33 and other endogenous molecules have deleterious effects on joints, and can recruit immune cells such as dendritic cells to inflamed synovia, initiating the adaptive immune response and perpetuating disease. Improving our understanding of the pathological mechanisms associated with these danger signals is important to enable the targeting of new therapeutic approaches for arthritis.
108 citations
TL;DR: Manganese dioxide nanoparticles with physicochemical properties that facilitate their uptake into cartilage demonstrated chondroprotection of cytokine-challenged cartilage explants by reducing the loss of glycosaminoglycans and release of nitric oxide and Quantitative PCR analysis revealed that the particles mitigated impacts of oxidative stress related genes in cytokineschallenged chond rocytes.
103 citations
References
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TL;DR: R-Hu-EPO also ameliorates the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis, and the toxicity of kainate, and clinical trials evaluating systemically administered r-Hu -EPO as a general neuroprotective treatment are warranted.
Abstract: ‡§ ¶ Erythropoietin (EPO), recognized for its central role in erythropoiesis, also mediates neuroprotection when the recombinant form (r-HuEPO) is directly injected into ischemic rodent brain. We observed abundant expression of the EPO receptor at brain capillaries, which could provide a route for circulating EPO to enter the brain. In confirmation of this hypothesis, systemic administration of r-Hu-EPO before or up to 6 h after focal brain ischemia reduced injury by ’50‐75%. R-Hu-EPO also ameliorates the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis, and the toxicity of kainate. Given r-Hu-EPO’s excellent safety profile, clinical trials evaluating systemically administered r-HuEPO as a general neuroprotective treatment are warranted.
1,439 citations
"The Roles of Mechanical Stresses in..." refers background in this paper
...In addition, pilot studies have shown that much of the injuryrelated loss of ATP can be avoided by early treatment with ARA290, which stimulates glycolysis and opposes catabolic signaling through activation of the Akt pathway.(82,83,85,86,88-90) This suggests that ARA290 could be a useful adjunct therapy to rescue cells from trauma-induced metabolic impairment....
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1,325 citations
TL;DR: The authors used data from the United States first national Health and Nutrition Examination Survey of 1971-1975 (HANES I) to explore the cross-sectional associations between radiographic osteoarthritis of the knee and a variety of putative risk factors, and found significant associations of knee osteoartritis with overweight, race, and occupation.
Abstract: The authors used data from the United States first national Health and Nutrition Examination Survey of 1971-1975 (HANES I) to explore the cross-sectional associations between radiographic osteoarthritis of the knee and a variety of putative risk factors. A total of 5,193 black and white study participants aged 35-74 years, 315 of whom had x-ray-diagnosed osteoarthritis of the knee, were available for analysis. After controlling for confounders, the authors found significant associations of knee osteoarthritis with overweight, race, and occupation, all of which have been suggested by smaller cross-sectional studies. They then focused specifically on those factors. For overweight, they found a strong association between current obesity and osteoarthritis of the knee, with a dose-response effect not previously assessed. This association was also seen for self-reported minimum adult weight, a proxy for long-term obesity, and was present in persons with asymptomatic osteoarthritis of the knee. These findings strongly suggest that obesity is causative. HANES I was the first study in which racial differences in osteoarthritis of the knee could be assessed within the same country. The black women who were studied had an increased risk of disease (odds ratio (OR) = 2.12, 95% confidence interval (CI) = 1.39-3.23) after controlling for age and weight, although the black men did not. Finally, the authors used the US Department of Labor Dictionary of Occupational Titles to obtain characterizations of the physical demands and knee-bending stress associated with occupations and to study the relation between physical demands of jobs and osteoarthritis of the knee. They found for persons aged 55-64 years an association between knee-bending demands and osteoarthritis of the knee (men, OR = 2.45, 95% CI = 1.21-4.97; women, OR = 3.49, 95% CI = 1.22-10.52). Since such occupational physical demands are common, the authors conclude that they may be associated with a substantial proportion of osteoarthritis of the knee.
891 citations
TL;DR: CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.
Abstract: Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype-selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyelitis at a potency and efficacy comparable to EPO.
807 citations