Cysteine proteinase cathepsin K mRNA 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 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.


CONCLUSIONS
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.
Center for Experimental Rheumatology, Department of Rheumatology, University Hospital, Zürich, Switzerland.
K M
KM
Hummel
P K
PK
Petrow
J K
JK
Franz
U
U
Müller-Ladner
W K
WK
Aicher
R E
RE
Gay
D
D
Brömme
S
S
Gay
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000378:metabolism; D001842:Bone and Bones / Q000201:enzymology / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000201:enzymology* / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002401:Cathepsin B; D056657:Cathepsin K; D002403:Cathepsins; D003094:Collagen; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C534130:CTSK protein, human