Osteoarthritis is characterized by focal cartilage destruction and marked formation of osteophytes. We have investigated the possible relationship between site specific occurrence of cartilage damage and osteophytes in the collagenase induced murine osteoarthritis model. The degree of instability of the joint correlated with the amount of cartilage loss. Moreover, cartilage damage in the medial tibial plateau correlated only strongly with the osteophyte at the medial plateau, whereas a similar, site directed trend was noted for lateral damage and lateral osteophytes. A separate study with intraarticular injection of TGF beta 1 in normal murine knee joints revealed that this factor can induce osteophytes at characteristic sites, suggesting a role of endogenous TGF beta in this phenomenon.