Tian Hua, Stogiannidis Ioannis
Department of Orthopaedics, Peking University Third Hospital, Beijing 100083, China.
Acta Biochim Biophys Sin (Shanghai). 2006 Oct;38(10):677-82. doi: 10.1111/j.1745-7270.2006.00218.x.
Cartilage oligomeric matrix protein (COMP) strengthens cartilage by binding to type II and type IX collagen-forming bridges between collagen fibrils. It was hypothesized that perhaps one or more anabolic growth factors such as insulin-like growth factor-I (IGF-I), fibroblast growth factor-1 (FGF-1) or platelet derived growth factor-BB (PDGF-BB) increase COMP gene expression. Their effects on primary human chondrocytes and the chondrogenic cell line ATDC5 were studied using real time reverse transcript-polymerase chain reaction (RT-PCR) for quantification. IGF-I, but not the FGF-1 or PDGF-BB, up-regulated COMP gene expression by approximate 5-fold in human adult chondrocytes in a dose- and time-dependent manner. IGF-I exerted similar effects on ATDC5 cells. Results from these real time RT-PCR experiments were confirmed by transfecting into ATDC5 cells a full-length mouse COMP promoter cloned upstream of a luciferase reporter gene. On stimulation with IGF-I, the luciferase reporter activity increased by about eight times. In conclusion, IGF-I seems to be an important positive regulator of COMP, which may play an important role in an attempted repair of either traumatized or degenerated cartilage.
软骨寡聚基质蛋白(COMP)通过与II型和IX型胶原结合,在胶原纤维之间形成桥梁,从而强化软骨。研究假设,或许一种或多种合成代谢生长因子,如胰岛素样生长因子-I(IGF-I)、成纤维细胞生长因子-1(FGF-1)或血小板衍生生长因子-BB(PDGF-BB),会增加COMP基因的表达。使用实时逆转录聚合酶链反应(RT-PCR)进行定量研究,观察它们对原代人软骨细胞和软骨形成细胞系ATDC5的影响。IGF-I而非FGF-1或PDGF-BB,在成人软骨细胞中以剂量和时间依赖性方式使COMP基因表达上调约5倍。IGF-I对ATDC5细胞也有类似作用。将克隆于荧光素酶报告基因上游的全长小鼠COMP启动子转染至ATDC5细胞,证实了这些实时RT-PCR实验的结果。用IGF-I刺激后,荧光素酶报告基因活性增加约8倍。总之,IGF-I似乎是COMP的重要正向调节因子,这可能在创伤或退变软骨的修复尝试中发挥重要作用。