Abstract:In contrast to collagen II and matrilin-3, COMP lacks the ability to trigger a proinflammatory response in chondrocytes, although it carries an RGD motif and can bind to integrins. COMP is a well-accepted biomarker for osteoarthritis but increased COMP levels do not necessarily correlate with inflammation.
“…The inflammatory potential of marathon running as previously shown (Nickel, Emslander, et al, 2012) may influence tissue metabolism and may hence be an important factor for long-term effects of marathon running. Because COMP lacks the ability to trigger a proinflammatory response in chondrocytes (Ruthard et al, 2014), increased serum COMP in slower runners may rather result from than cause the greater release of hsCRP in these participants. We included only runners without any preclinical inflammation.…”
Section: Marathon Finishing Time Pro-inflammatory and Cartilage Biommentioning
“…The inflammatory potential of marathon running as previously shown (Nickel, Emslander, et al, 2012) may influence tissue metabolism and may hence be an important factor for long-term effects of marathon running. Because COMP lacks the ability to trigger a proinflammatory response in chondrocytes (Ruthard et al, 2014), increased serum COMP in slower runners may rather result from than cause the greater release of hsCRP in these participants. We included only runners without any preclinical inflammation.…”
Section: Marathon Finishing Time Pro-inflammatory and Cartilage Biommentioning
“…Treatment of primary human chondrocytes with fragments of collagen II as well as the collagen associated protein matrilin-3 induced a concentration- and time-dependent release of interleukin (IL)-1, -6, -8, TNFα and MMP-1, -3, -13 [ 80 ]. Interestingly, larger fragments of COMP have not been able to do so in identical in vitro experiments [ 81 ]. Very recently, the effect of smaller COMP-derived peptides that have been detected in the degenerated cartilage tissue of OA patients was studied in different in vitro assays.…”
Section: The Role Of Proteases and Cytokines In Oamentioning
Although osteoarthritis (OA) is the most common musculoskeletal condition that causes significant health and social problems worldwide, its exact etiology is still unclear. With an aging and increasingly obese population, OA is becoming even more prevalent than in previous decades. Up to 35% of the world’s population over 60 years of age suffers from symptomatic (painful, disabling) OA. The disease poses a tremendous economic burden on the health-care system and society for diagnosis, treatment, sick leave, rehabilitation, and early retirement. Most patients also experience sleep disturbances, reduced capability for exercising, lifting, and walking and are less capable of working, and maintaining an independent lifestyle. For patients, the major problem is disability, resulting from joint tissue destruction and pain. So far, there is no therapy available that effectively arrests structural deterioration of cartilage and bone or is able to successfully reverse any of the existing structural defects. Here, we elucidate novel concepts and hypotheses regarding disease progression and pathology, which are relevant for understanding underlying the molecular mechanisms as a prerequisite for future therapeutic approaches. Emphasis is placed on topographical modeling of the disease, the role of proteases and cytokines in OA, and the impact of the peripheral nervous system and its neuropeptides.
“…The 3 peptides reported originate from the multifunctional C-terminal domain of COMP, which plays diverse roles in cartilage homeostasis, 11 inflammation, 12 and transforming growth factor-β (TGF-β) signaling. 13 , 14 Previous research found that full-length COMP was unable to modify the expression of proinflammatory markers in cartilage, 15 unlike its binding partner MATN3 and its fragments. 16 However, we hypothesized that those COMP fragments released by cartilage could have an OA-relevant biological function.…”
Objective To evaluate if 3 peptides derived from the cartilage oligomeric matrix protein (COMP), which wounded zones of cartilage secrete into synovial fluid, possess biological activity and might therefore be involved in the regulation of specific aspects of joint regeneration. Methods The 3 peptides were produced by chemical synthesis and then tested in vitro for known functions of the COMP C-terminal domain from which they derive, and which are involved in osteoarthritis: transforming growth factor-β (TGF-β) signaling, vascular homeostasis, and inflammation. Results. None of the peptides affected the gene expression of COMP in osteochondral progenitor cells ( P > 0.05). We observed no effects on the vascularization potential of endothelial cells ( P > 0.05). In cultured synovium explants, no differences on the expression of catabolic enzymes or proinflammatory cytokines were found when peptides were added ( P > 0.05). Discussion and Conclusions The 3 peptides tested do not regulate TGF-β signaling, angiogenesis and vascular tube formation, or synovial inflammation in vitro and therefore most likely do not play a major role in the disease process.
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