Cartilage oligomeric matrix protein (COMP) strengthens cartilage by binding to type Ⅱ and typeⅨ 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.