The effects of dexamethasone in vitro on the production of collagenase and inhibitor by synovial and cartilage explants from the joints of rabbits with a proliferative arthritis.
Using a rabbit model arthritis we have investigated the ability of dexamethasone to alter the production of collagenase and the specific metallo-proteinase inhibitor TIMP by explants of synovium and cartilage in vitro. The patterns of collagenase and TIMP production by untreated explants from arthritic joint tissues in culture were similar to those described previously [1, 2]. Dexamethasone dramatically altered the patterns of production of collagenase and TIMP. At a dose of 10 nM, or above, the patterns of production by treated synovium resembled those of normal rabbit synovium: collagenase production was suppressed and TIMP increased compared with untreated arthritic synovium. The levels of latent collagenase in cartilage also fell with increasing doses of dexamethasone and TIMP levels were higher, although normal levels were not reached. These experiments have been conducted as a prelude to testing the effects of various anti-rheumatic drugs in vivo, and attempting to correlate changes in clinical parameters with the subsequent production of collagenase and TIMP in vitro. The data are discussed in relation to the therapeutic use of corticosteroids and to their mode of action on joint tissues.
D000818:Animals; D001168:Arthritis / Q000201:enzymology* / Q000473:pathology; D002358:Cartilage, Articular / Q000201:enzymology* / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011817:Rabbits; D013583:Synovial Membrane / Q000201:enzymology* / Q000473:pathology; D019714:Tissue Inhibitor of Metalloproteinases
D004791:Enzyme Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D003907:Dexamethasone; D003012:Microbial Collagenase