CYSTEINE PROTEINASE CATHEPSIN-K MESSENGER-RNA IS EXPRESSED IN SYNOVIUM OF PATIENTS WITH RHEUMATOID-ARTHRITIS AND IS DETECTED AT SITES OF SYNOVIAL BONE DESTRUCTION

Objective. Cysteine proteinases B and L have been shown to be involved in matrix degradation of joints in patients with rheumatoid arthritis (RA). Since the cysteine proteinase cathepsin K is assumed to play a pivotal role in osteoclast mediated bone resorption, we investigated t he expression of cathepsin K in RA joints. Methods. We studied 10 RA a nd 4 normal synovial specimens and 5 articular heads with RA lesions b y in situ hybridization, applying specific riboprobas for cathepsin K, human collagen type I, and cathepsin B. Antibodies against monocyte/m acrophage associated CD68 antigen were applied in immunohistochemistry . Reverse transcription-polymerase chain reaction (RT-PCR) and ribonuc lease protection assay (RPA) were performed on 4 RA, 1 normal, and 1 i mmortalized normal fibroblast cultures. Results. Cathepsin K mRNA expr ession was upregulated in RA synovium compared to normal synovium. Cat hepsin K mRNA was expressed mainly by synovial fibroblasts. These data were con firmed by RT-PCR and RPA. In RA articular heads, cathepsin K mRNA was detected at sites where synovium attached and invaded underl ying bone. The cells at these sites represented collagen type I and ca thepsin B mRNA expressing fibroblasts as well as CD68+ macrophages and giant cells. In addition, a distinct expression of cathepsin K mRNA w as also detected around lymphocytic infiltrates in RA synovium. Conclu sion. The data indicate that cathepsin K is not only expressed by oste oclasts but also by synovial fibroblasts, and suggest that cathepsin K contributes to bone destruction mediated by RA synovial cells. The ex pression of cathepsin K around lymphocytic infiltrates suggests furthe r to facilitate the movement of mononuclear cells through the perivasc ular interstitial matrix and thereby contribute to interstitial matrix turnover.