Rheumatic disorders are common complications in patients on long-term hemodialysis (HD), and abnormalities of collagen metabolism in the musculoskeletal system have been suggested in these patients. Since collagenase, which catalyzes the initial step in the proteolytic degradation of collagen, plays an important role in the metabolism of collagen, the present study investigated whether factor(s) present in the sera from patients on long-term HD stimulates collagenase gene expression in synovial cells. The addition of sera from 8 patients on long-term HD resulted in 1.5- to 4.0-fold increases in the collagenase mRNA level in human synovial cells as compared with that of sera from normal subjects. The collagenase-inducing factor(s) in uremic sera is more than 3,000 D in molecular mass and shows no binding to heparin. Uremic sera also increased stromelysin mRNA, but failed to exert any effect on mRNAs for tissue inhibitor of metalloproteinases and proαl(I)collagen. Our findings suggest that there exists a factor(s) to enhance degradation of synovial collagen in sera from long-term HD patients