The effects of razoxane (ICRF 159) on the production of collagenase and inhibitor (TIMP) by stimulated rabbit articular chondrocytes.
Monolayer cultures of rabbit chondrocytes were stimulated to produce collagenase with conditioned medium from human peripheral blood mononuclear cells (MCM), and the ability of Razoxane to modulate the production of collagenase and specific tissue inhibitor of metalloproteinases (TIMP) was studied. Collagenase production was inhibited and TIMP increased by Razoxane, in a dose-dependent manner, when cells were treated daily for 3 days. Over this period the effect of Razoxane was progressive; 50 micrograms/ml or less had no effect at day 1 but 50 micrograms/ml was effective by day 3. The effectiveness of Razoxane was inversely related to the degree of MCM stimulation and the confluency of the culture. On removal of the drug, chondrocytes stimulated with MCM recovered their ability to produce collagenase, and TIMP production returned to near normal. The results suggest that the ability of Razoxane to reduce collagenase and increase TIMP production may correlate with its effectiveness in treating psoriatic arthritis.
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D002478:Cells, Cultured; D010450:Endopeptidases / Q000096:biosynthesis; D006801:Humans; D008666:Metalloendopeptidases; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010879:Piperazines / Q000494:pharmacology*; D011480:Protease Inhibitors; D011817:Rabbits; D011929:Razoxane / Q000494:pharmacology*
D010879:Piperazines; D011480:Protease Inhibitors; D011929:Razoxane; D010450:Endopeptidases; D008666:Metalloendopeptidases; D003012:Microbial Collagenase