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.
Hummel
K M
KM
Center for Experimental Rheumatology, Department of Rheumatology, University Hospital, Zürich, Switzerland.
Petrow
P K
PK
Franz
J K
JK
Müller-Ladner
U
U
Aicher
W K
WK
Gay
R E
RE
Brömme
D
D
Gay
S
S
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