Hummel K M, Petrow P K, Franz J K, Müller-Ladner U, Aicher W K, Gay R E, Brömme D, Gay S
Center for Experimental Rheumatology, Department of Rheumatology, University Hospital, Zürich, Switzerland.
J Rheumatol. 1998 Oct;25(10):1887-94.
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.
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.
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.
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.
半胱氨酸蛋白酶B和L已被证明参与类风湿性关节炎（RA）患者关节的基质降解。由于半胱氨酸蛋白酶组织蛋白酶K被认为在破骨细胞介导的骨吸收中起关键作用，我们研究了组织蛋白酶K在RA关节中的表达。
我们通过原位杂交研究了10个RA和4个正常滑膜标本以及5个有RA病变的关节头，应用针对组织蛋白酶K、人I型胶原和组织蛋白酶B的特异性核糖探针。抗单核细胞/巨噬细胞相关CD68抗原的抗体用于免疫组织化学。对4个RA、1个正常和1个永生化正常成纤维细胞培养物进行逆转录聚合酶链反应（RT-PCR）和核糖核酸酶保护试验（RPA）。
与正常滑膜相比，RA滑膜中组织蛋白酶K mRNA表达上调。组织蛋白酶K mRNA主要由滑膜成纤维细胞表达。这些数据通过RT-PCR和RPA得到证实。在RA关节头中，在滑膜附着并侵入下方骨的部位检测到组织蛋白酶K mRNA。这些部位的细胞代表表达I型胶原和组织蛋白酶B mRNA的成纤维细胞以及CD68+巨噬细胞和巨细胞。此外，在RA滑膜的淋巴细胞浸润周围也检测到组织蛋白酶K mRNA的明显表达。
数据表明组织蛋白酶K不仅由破骨细胞表达，也由滑膜成纤维细胞表达，并提示组织蛋白酶K促成RA滑膜细胞介导的骨破坏。组织蛋白酶K在淋巴细胞浸润周围的表达进一步提示其促进单核细胞通过血管周围间质基质的移动，从而促成间质基质更新。
