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Review
. 2012 Jan;347(1):257-65.
doi: 10.1007/s00441-011-1194-6. Epub 2011 Jun 4.

Age-dependent alteration of TGF-β signalling in osteoarthritis

Peter M van der Kraan  1 , Marie-José Goumans, Esmeralda Blaney Davidson, Peter ten Dijke
Affiliations
Review

Age-dependent alteration of TGF-β signalling in osteoarthritis

Peter M van der Kraan et al. Cell Tissue Res. 2012 Jan.

Abstract

Osteoarthritis (OA) is a disease of articular cartilage, with aging as the main risk factor. In OA, changes in chondrocytes lead to the autolytic destruction of cartilage. Transforming growth factor-β has recently been demonstrated to signal not only via activin receptor-like kinase 5 (ALK5)-induced Smad2/3 phosphorylation, but also via ALK1-induced Smad1/5/8 phosphorylation in articular cartilage. In aging cartilage and experimental OA, the ratio ALK1/ALK5 has been found to be increased, and the expression of ALK1 is correlated with matrix metalloproteinase-13 expression. The age-dependent shift towards Smad1/5/8 signalling might trigger the differentiation of articular chondrocytes with an autolytic phenotype.

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Figures

Fig. 1
Fig. 1
Transforming growth factor-β (TGF-β) plays a role in key characteristics of osteoarthritis (OA): cartilage damage, osteophyte formation and synovial fibrosis. TGF-β is required for the maintenance of healthy cartilage during which it signals primarily via Smad2/3. With age and OA, a shift in the activin receptor-like kinase 5 (ALK5):ALK1 ratio is established, favouring Smad1/5/8 signalling and leading to a loss of the cartilage protective role of Smad2/3. We suggest a role for this balance shift towards ALK1 in cartilage damage during OA development. In addition, TGF-β is a crucial factor in the onset of osteophyte development. In later stages of osteophyte development, bone morphogenetic proteins (BMP) might be equally important. TGF-β is a major player in fibrotic diseases and, during OA, it induces synovial fibrosis
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