Cysteine proteinase activity in the development of arthritis in an adjuvant model of the rat

Abstract

Cathepsin B and L activity was studied histochemically in arthritic rat ankle joints using specific synthetic substrates in a post coupling method on unfixed and undecalcified cryostat sections of rat ankle joints. Activity was strongly increased in chondrocytes and cells of the inflamed synovium with the development of arthritis induced by the synthetic adjuvant CP20961. Activity reached a maximum 20 days after induction of arthritis and decreased as the rats entered natural remission. Cathepsin B and L were at their highest level when macrophages were present in the joint space, as shown by using monoclonal antibody markers for rat macrophages (ED1 and ED2) in a biotin-avidin immunoperoxidase assay. This suggests that the macrophage infiltrate may have stimulated proteinase production in chondrocytes through cytokine release. The profile of appearance of cysteine proteinases suggests their involvement in the breakdown of cartilage and bone in the arthritic joint.

Synovial tissue protease gene expression and joint erosions in early rheumatoid arthritis

“…They are up-regulated by IL-1 and TNF␣ (47), are present at high levels in RA synovial fluid (16), and have been immunolocalized to synovial cells attached to the cartilage and bone (14,18). Experimental models of arthritis demonstrate that levels of these proteases rise with disease progression (19), while specific inhibitors help ameliorate joint inflammation and articular destruction (20,21). Although CB and CL are similar enzymes, they have been shown to act on collagen fibers through distinct mechanisms.…”

“…CB and CL are present in increased quantities in RA synovial fluid (16) and have been identified in several cell types in the RA synovial membrane (17), particularly at sites of bone and cartilage erosion (14,18). Their levels have been found to parallel disease activity in an animal model of arthritis (19), while selective cysteine protease inhibitors decrease the severity of experimental arthritis (20,21).…”

Expression of matrix metalloproteinase 9 (96‐kd gelatinase B) in human rheumatoid arthritis

“…Further support for the role of MMPs in the pathogenesis of inflammatory arthritis as related to connective tissue turnover can be demonstrated in experimental animal models. Immunolocalization studies in animal models of inflammatory arthritis have focused on MMP-1, MMP-3, and MMP-9, as well as other proteinases (23, 24,54,55). MMPs have been identified in inflamed periarticular tissue, and their expression has been correlated with the loss of joint architecture (23,24).…”

Cathepsin B in gingival crevicular fluid of adult periodontitis patients: Identification by immunological and enzymological methods

“…This enzyme is also thought to play important roles in the initiation and perpetuation of inflammatory processes [3][4][5][6][7][8][9][10], since it: 1) degrades extracellular matrix proteins such as collagens *Present address: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA Correspondence to: E. Ichimaru between natural and weak acidic pH, 2) modulates various inflammatory mediators, and 3) is released extracellularly by inflammatory stimulation. Moreover this enzyme is one of the available marker enzymes reflecting the clinical state of inflammatory diseases [11][12][13], such as sepsis, peritonitis and chronic arthritis.…”