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
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
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DOI：
10.1136/ard.60.3.254
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发表时间：
2001-03-01
影响因子：
27.4
通讯作者：
Cawston, T
中科院分区：
文献类型：
--
作者：
Hui, W;Rowan, AD;Cawston, T
目的：探讨胰岛素样生长因子1(IGF1)对促炎细胞因子IL 1α联合抑癌素M(OSM)诱导牛鼻软骨和原代人关节软骨细胞胶原释放及基质金属蛋白酶(MMPs)产生和表达的影响。羟脯氨酸测定法测定胶原释放量。胶原酶活性测定采用H-3乙酰化胶原纤维扩散法。结果IGF1能部分抑制IL1α或IL1α+OSM诱导的牛鼻软骨胶原释放。伴随而来的是牛鼻软骨胶原酶的分泌和激活减少。IGF1还可下调IL1α或IL1α+OSM诱导的人关节软骨细胞和牛软骨细胞中MMP1、MMP3、MMP8和MMP13mRNA的表达。对软骨细胞TIMP-1mRNA的产生和表达无明显影响。结论：本研究首次发现IGF1可部分阻断软骨中胶原的释放，提示IGF1下调胶原酶的表达可能是其抑制促炎细胞因子诱导的软骨吸收的重要机制之一。
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.