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

Physiological loading of articular cartilage maintains transforming growth factor-β (TGFβ) signalling and prevents hypertrophic differentiation of articular chondrocytesTGFβ signalling changes with ageing, at least in animal models, resulting in a loss of SMAD2–SMAD3 signalling and making articular cartilage prone to changes associated with osteoarthritis (OA)Loading-induced induction of TGFβ signalling is less efficient in aged cartilage than in young cartilage, impairing the mechanism that blocks chondrocyte hypertrophic differentiationDuring OA, high levels of active TGFβ in the joint drive fibrosis, osteophyte formation and subchondral bone changesThe role of TGFβ changes from protective in a young, healthy joint to pathologic in an osteoarthritic joint