The changing role of TGFβ in healthy, ageing and osteoarthritic joints.

Transforming growth factor-β (TGFβ) is a pleiotropic cytokine that is important in the regulation of joint homeostasis and disease. TGFβ signalling is induced by loading and has an important function in maintaining the differentiated phenotype of articular chondrocytes. Concentrations of active TGFβ differ greatly between healthy and osteoarthritic joints, being low in healthy joints and high in osteoarthritic joints, leading to the activation of different signalling pathways in joint cells. The characteristic pathology of osteoarthritic joints, such as cartilage damage, osteophyte formation and synovial fibrosis, seems to be stimulated or even caused by the high levels of active TGFβ, in combination with altered chondrocyte signalling pathways (which are also observed in ageing joints). In this Review, the changing role of TGFβ in normal joint homeostasis, ageing and osteoarthritis is discussed: TGFβ counteracts pathological changes in a young healthy joint, alters its signalling during ageing and is a driving force of pathology in osteoarthritic joints.