Matrix metalloproteinases (MMPs) have been implicated to play an important role in degradation of cartilage matrix, and elevated levels of MMPs have been detected in synovial tissue, synovial fluid and serum from rheumatoid arthritis (RA) patients. The mechanisms of cartilage destruction in RA, however, have not been clearly elucidated. Overexpression of tissue inhibitor of MMPs type 1 (TIMP-1) in the collagen-induced arthritis (CIA) mouse and in the tumor necrosis factor (TNF)-a transgenic mouse has very different effects. In the case of CIA mice, TIMP-1 cannot prevent the destruction of cartilage matrix and even increases the severity of inflammation in arthritic joints (see Additional information). This study investigated the effects of TIMP-1 overexpression in TNF-a transgenic mice.