Pathology and treatment for osteoarthritis-efficient use of endogenous insulin-like growth factor-1

本研究旨在阐明胰岛素样生长因子(IGF)- 1对软骨代谢的影响，并探讨其治疗骨关节炎的方法。将igf -1添加到有/不含白细胞介素(IL)-1或地塞米松的人关节软骨细胞培养基中。提取细胞层总RNA，采用RT-PCR和real - time-PCR检测聚集蛋白、II型胶原、基质金属蛋白酶（MMP）、IGF-I、IGF-I结合蛋白和IGF-I受体mRNA的表达。igf - 1诱导了聚集蛋白和II型胶原mRNA的表达，而il - 1和地塞米松对聚集蛋白mRNA表达的抑制作用略有减弱。igf - 1对MMP-3、-9、13的表达无明显影响。进一步IL-1诱导igf -1的表达，但降低igf -受体的表达。相反，地塞米松诱导IGF-1受体表达，但降低IGF-1的表达。igf -1和地塞米松也能调节igf -1结合蛋白mRNA的表达。这些发现表明，igf -1促进软骨基质的合成，并保护关节软骨免受降解。igf - 1可能是治疗骨关节炎的候选药物之一。

The aim of this study was to clarify the effects of insulin-like growth factor (IGF)-I on cartilage metabolism, and finally to investigate the treatment for osteoarthritis. IGF-I was added to the culture medium of human articular chondrocytes with/without interleukin (IL)-1 or dexamethasone. Total RNA was extracted from the cell layer, and mRNA expression for aggrecan, type II collagen, matrix metalloprotease (MMP), IGF-I, IGF-binding proteins, and IGF-I receptor was examined using RT-PCR and real time-PCR. IGF-I induced the expression of aggrecan and type II collagen mRNA, and slightly decreased the inhibitory effect of IL-I or dexamethasone on mRNA expression for aggrecan. IGF-I showed little effects on MMP-3, -9, 13 expression. Further IL-1 induced the expression of IGF-I but decreased IGF-receptor. On the contrary, dexamethasone induced IGF-1 receptor but decreased IGF-I expression. mRNA expression for IGF-binding proteins was also regulated by both f IL-1 and dexamethasone These findings suggest that IGF-I promote synthesis of cartilage matrix, and protect articular cartilage from degradation. IGF-I might be one of the candidates for treatment of osteoarthritis.