Expression of the tissue inhibitor of metalloproteinases (TIMP) gene family in normal and osteoarthritic joints

The pathophysiological and biological significance of tissue inhibitor of t he metalloproteinases-3 (TIMP-3) gene compared to other TIMPs was investiga ted in osteoarthritic (OA) human and normal bovine joint tissues. Human OA synovial fibroblasts in culture constitutively expressed TIMP mRNAs. TIMP-3 , TIMP-1 and gelatinase A mRNAs were elevated in most human OA synovia over controls, while TIMP-2 expression was similar. TIMP-3 and TIMP-1 mRNAs pre sent in bovine cartilage were inducible by serum factors. Transforming grow th factor beta (TGF-beta 1) induced TIMP-3 RNA and protein in human OA and normal bovine chondrocytes. TIMP mRNAs were low (TIMP-1) or undetectable in human fetal chondrocytes but were expressed at all other ages. Thus, the t wo main joint tissues, synovial membranes and cartilage, express TIMP genes . Due to their matrix protecting activities, the presence of multiple TIMPs may be beneficial for normal joints, while increased TIMP-3 and TIMP-1 exp ression in arthritic joints may be associated with pathological remodeling.