A signaling feedback loop that contributes to cartilage degeneration may offer a fruitful target for the treatment of osteoarthritis. During the early stages of this disorder, cartilage-forming chondrocytes undergo a process of expansion known as hypertrophy, after which they die and are replaced by calcium. Researchers led by Peiqiang Su and Dongsheng Huang of Sun Yat-sen University have demonstrated that COL2A1, an important structural protein, represents an important safeguard against hypertrophy. COL2A1 helps maintain chondrocytes in their normal, healthy state, but Su and Huang showed that signaling factors produced during cartilage repair can reduce COL2A1 levels. This in turn accelerates hypertrophy, promoting further depletion of COL2A1 and ultimately leading to full-blown osteoarthritis. Drugs that break this cycle and preserve COL2A1 could thus help protect endangered joints before the damage becomes severe.