title: Collagenolytic systems in rheumatoid arthritis.
abstract: As the proliferative lesion of rheumatoid arthritis becomes polarized and invasion of articular cartilage and subchondral bone begins, it is likely that many mesenchymal cells, including periosteal and perichondral cells, and perhaps even the chondrocytes and osteoblasts themselves can be activated to produce destructive enzymes. Early in the course of RA cartilage proteoglycans are depleted, leaving the remaining collagen more susceptible to mechanical breakdown as well as to enzymatic breakdown. Specific collagenases are released by synovial cells and, in addition, by polymorphonuclear leukocytes. The latter enzyme may account for free collagenase found in synovial fluid, a finding possibly related to saturation of inhibitory proteins by proteases with greater affinity for them, leaving collagenase active. At this time in the course of rheumatoid arthritis, a joint would be under double jeopardy from enzymes released by the invading pannus as well as by collagenase free and active in the synovial fluid. Rapid destruction could occur. Although cartilage collagen has an intrinsic resistance to collagenase conferred by its primary structure and by higher order structure (e.g. intermolecular cross-links), it seems wise to cool down hot joints because increased temperature may increase the rate of collagen degradation and, therefore, cartilage destruction. In addition, superimposed sepsis or acute flares of rheumatoid disease result in enough influx of polymorphonuclear leukocytes into the joints to result in free collagenolytic activity being present. This provides a rationale for frequent aspiration of any joint fluid, septic or otherwise, containing high polymorphonuclear leukocyte counts.
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology*; D001769:Blood; D002358:Cartilage, Articular / Q000473:pathology; D055598:Chemical Phenomena; D002621:Chemistry; D003094:Collagen / Q000378:metabolism*; D003593:Cytoplasm / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D005260:Female; D005384:Finger Joint / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D006225:Hand / Q000000981:diagnostic imaging; D006801:Humans; D007595:Joint Prosthesis; D007958:Leukocyte Count; D008297:Male; D003012:Microbial Collagenase / Q000378:metabolism / Q000494:pharmacology; D011859:Radiography; D012218:Rheumatoid Nodule / Q000473:pathology; D013582:Synovial Fluid / Q000201:enzymology; D013583:Synovial Membrane / Q000201:enzymology; D013696:Temperature; D014357:Trypsin / Q000494:pharmacology
chemical_list: D003094:Collagen; D014357:Trypsin; D003012:Microbial Collagenase