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Arthritis Research & Therapy

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01.02.2010 | Review

A role for age-related changes in TGFβ signaling in aberrant chondrocyte differentiation and osteoarthritis

verfasst von: Peter M van der Kraan, Esmeralda N Blaney Davidson, Wim B van den Berg

Erschienen in: Arthritis Research & Therapy | Ausgabe 1/2010

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Abstract

Transforming growth factor beta (TGFβ) is a growth factor with many faces. In our osteoarthritis (OA) research we have found that TGFβ can be protective as well as deleterious for articular cartilage. We postulate that the dual effects of TGFβ on chondrocytes can be explained by the fact that TGFβ can signal via different receptors and related Smad signaling routes. On chondrocytes, TGFβ 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 TGFβ 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 TGFβ 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 TGFβ signaling in OA development.

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Titel: A role for age-related changes in TGFβ signaling in aberrant chondrocyte differentiation and osteoarthritis
verfasst von: Peter M van der Kraan
Esmeralda N Blaney Davidson
Wim B van den Berg
Publikationsdatum: 01.02.2010
Verlag: BioMed Central
Erschienen in: Arthritis Research & Therapy / Ausgabe 1/2010
Elektronische ISSN: 1478-6362
DOI: https://doi.org/10.1186/ar2896

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