Cysteine proteinase cathepsin K mRNA is expressed in synovium of patients with rheumatoid arthritis and is detected at sites of synovial bone destruction

Klaus M. Hummel, Peter K. Petrow, Juliane K. Franz, Ulf Müller-Ladner, Wilhelm K. Aicher, Renate E. Gay, Dieter Brömme, Steffen Gay

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

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 the expression of cathepsin K in RA joints. Methods. We studied 10 RA and 4 normal synovial specimens and 5 articular heads with RA lesions by in situ hybridization, applying specific riboprobes for cathepsin K, human collagen type I, and cathepsin B. Antibodies against monocyte/macrophage associated CD68 antigen were applied in immunohistochemistry. Reverse transcription-polymerase chain reaction (RT-PCR) and ribonuclease protection assay (RPA) were performed on 4 RA, 1 normal, and 1 immortalized normal fibroblast cultures. Results. Cathepsin K mRNA expression was upregulated in RA synovium compared to normal synovium. Cathepsin K mRNA was expressed mainly by synovial fibroblasts. These data were confirmed by RT-PCR and RPA. In RA articular heads, cathepsin K mRNA was detected at sites where synovium attached and invaded underlying bone. The cells at these sites represented collagen type I and cathepsin B mRNA expressing fibroblasts as well as CD68+ macrophages and giant cells. In addition, a distinct expression of cathepsin K mRNA was also detected around lymphocytic infiltrates in RA synovium. Conclusion. The data indicate that cathepsin K is not only expressed by osteoclasts but also by synovial fibroblasts, and suggest that cathepsin K contributes to bone destruction mediated by RA synovial cells. The expression of cathepsin K around lymphocytic infiltrates suggests further to facilitate the movement of mononuclear cells through the perivascular interstitial matrix and thereby contribute to interstitial matrix turnover.

Original languageEnglish
Pages (from-to)1887-1894
Number of pages8
JournalJournal of Rheumatology
Volume25
Issue number10
StatePublished - Oct 1998

Keywords

  • Cathepsin K
  • Fibroblasts
  • Rheumatoid arthritis

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