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Báo cáo y học: "A role for age-related changes in TGFβ signaling in aberrant chondrocyte differentiation and osteoarthritis"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: A role for age-related changes in TGFβ signaling in aberrant chondrocyte differentiation and osteoarthritis. | van der Kraan et al. Arthritis Research Therapy 2010 12 201 http arthritis-research.eom content 12 1 201 REVIEW A role for age-related changes in TGFP signaling in aberrant chondrocyte differentiation and osteoarthritis Peter M van der Kraan Esmeralda N Blaney Davidson and Wim B van den Berg Abstract Transforming growth factor beta TGFP is a growth factor with many faces. In our osteoarthritis OA research we have found that TGFp can be protective as well as deleterious for articular cartilage. We postulate that the dual effects of TGFp on chondrocytes can be explained by the fact that TGFp can signal via different receptors and related Smad signaling routes. On chondrocytes TGFp not only signals via the canonical type I receptor ALK5 but also via the ALK1 receptor. Notably signaling via ALK5 Smad2 3 route results in markedly different chondrocyte responses than ALK1 signaling Smad1 5 8 and we postulate that the balance between ALK5 and ALK1 expression on chondrocytes will determine the overall effect of TGFp on these cells. Importantly signaling via ALK1 but not ALK5 stimulates MMP-13 expression by chondrocytes. In cartilage of ageing mice and in experimental OA models we have found that the ALK1 ALK5 ratio is significantly increased favoring TGFp signaling via the Smad1 5 8 route changes in chondrocyte differentiation and MMP-13 expression. Moreover human OA cartilage showed a significant correlation between ALK1 and MMP-13 expression. In this paper we summarize concepts in OA its link with ageing and disturbed growth factor responses and a potential role of TGFp signaling in OA development. Introduction Osteoarthritis OA is the joint disease with the highest incidence. The disease is in general divided into primary OA and secondary OA. Primary OA has no obvious Correspondence P.vanderkraan@reuma.umcn.nl Experimental Rheumatology Advanced Therapeutics NCMLS Radboud University Medical Centre Nijmegen Geert Grooteplein 28 6525 GA Nijmegen the Netherlands 2 BioMed .