Insulin-like growth factor 1 blocks collagen release and down regulates matrix metalloproteinase-1,-3,-8, and-13 mRNA expression in bovine nasal cartilage stimulated with oncostatin M in combination with interleukin 1 alpha

Objective-To investigate the effect of insulin-like growth factor 1 (IGF1) on the release of collagen, and the production and expression of matrix met alloproteinases (MMPs) induced by the proinflammatory cytokine interleukin 1 alpha (IL1 alpha) in combination with oncostatin M (OSM) from bovine nasa l cartilage and primary human articular chondrocytes. Methods-Human articular chondrocytes and bovine nasal cartilage were cultur ed with and without IGF1 in the presence of IL1 alpha or IL1 alpha + OSM. T he release of collagen was measured by an assay for hydroxyproline. Collage nase activity was determined with the diffuse fibril assay using H-3 acetyl ated collagen. The expression of MMP-1, MMP-3, MMP-8, MMP-13, and tissue in hibitor of metalloproteinase 1 (TIMP-1) mRNA was analysed by northern blot. Results-IGF1 can partially inhibit the release of collagen induced by IL1 a lpha or IL1 alpha + OSM from bovine nasal cartilage. This was accompanied b y a reduced secretion and activation of collagenase by bovine nasal cartila ge. IGF1 can also down regulate IL1 alpha or IL1 alpha + OSM induced MMP-1, MMP-3, MMP-8, and MMP-13 mRNA expression in human articular chondrocytes a nd bovine chondrocytes. It had no significant effect on the production and expression of TIMP-1 mRNA in chondrocytes. Conclusion-This study shows for the first time that IGF1 can partially bloc k the release of collagen from cartilage and suggests that down regulation of collagenases by IGF1 may be an important mechanism in preventing cartila ge resorption initiated by proinflammatory cytokines.