Dexamethasone inhibits collagen degradation induced by the combination of interleukin-1 and plasminogen in cartilage explant culture.
Glucocorticoids ameliorate erosion in animal osteoarthritis (OA) models and suppress synthesis of matrix metalloproteinases (MMP). However, in in vitro studies, their inhibitory effects on matrix degradation of cartilage have not been well documented by monitoring aggrecan. Collagen was monitored in this study to examine the effects of dexamethasone in cartilage explant culture. Dexamethasone clearly blocked collagen degradation induced by the combination of interleukin-1 (IL-1) and plasminogen at the concentration of 10(-9) M, which is much lower than the concentrations reportedly required to inhibit matrix synthesis. In addition, MMP-1 and MMP-3 were suppressed by dexamethasone treatment in a similar range of concentrations. The conversion of plasminogen to plasmin, however, was not blocked by treatment with dexamethasone. These results suggest that the inhibitory effect of dexamethasone on collagen degradation may be due to suppression of MMP production rather than suppression of fibrinolytic cascade. Thus, the ability of glucocorticoids to inhibit matrix degradation in vitro, which could be clearly shown by monitoring collagen degradation, may endorse their efficacy in animal OA models and suggest potential therapeutic effectiveness.
Saito
S
S
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan.
Katoh
M
M
Masumoto
M
M
Matsumoto
S
S
Masuho
Y
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002356:Cartilage / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions; D005343:Fibrinolytic Agents / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D010958:Plasminogen / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D011817:Rabbits
D000893:Anti-Inflammatory Agents; D005343:Fibrinolytic Agents; D007375:Interleukin-1; D020011:Protective Agents; D003907:Dexamethasone; D010958:Plasminogen; D003094:Collagen; D017364:Collagenases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1