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 1α

Objective-To investigate the effect of insulin-like growth factor 1 (IGF1) on the release of collagen, and the production and expression of matrix metalloproteinases (MMPs) induced by the proinflammatory cytokine interleukin 1 alpha (IL1 alpha) in combination with oncostatin M (OSM) from bovine nasal cartilage and primary human articular chondrocytes. Methods-Human articular chondrocytes and bovine nasal cartilage were cultured with and without IGF1 in the presence of IL1 alpha or IL1 alpha + OSM. The release of collagen was measured by an assay for hydroxyproline. Collagenase activity was determined with the diffuse fibril assay using H-3 acetylated collagen. The expression of MMP-1, MMP-3, MMP-8, MMP-13, and tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA was analysed by northern blot. Results-IGF1 can partially inhibit the release of collagen induced by IL1 alpha or IL1 alpha + OSM from bovine nasal cartilage. This was accompanied by a reduced secretion and activation of collagenase by bovine nasal cartilage. 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 and 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 block the release of collagen from cartilage and suggests that down regulation of collagenases by IGF1 may be an important mechanism in preventing cartilage resorption initiated by proinflammatory cytokines.