SMAD2 and osteoarthritis: With ageing, inevitable bone loss occurs, which is frequently the cause of osteoporosis, and inevitable bone and joint degeneration are observed, which often result in osteoarthrosis.48 TGF-β levels become excessively high in the blood stream of older people and ageing mice.49,50 In the ageing rodent models, p-Smad2/3-positive cells were significantly enhanced in the cartilage and subchondral bone.