Insulin-like growth factor I regulates apoptosis in condylar cartilage

Endogenous insulin-like growth factor-I (IGF-I) is known to affect the growth and development of condylar cartilage. However, the critical effect of IGF-I on cell survival is still unknown. We hypothesized that endogenous IGF-I could regulate the survival of cells of the mandibular condylar cartilage. Mandibular condyles dissected from 12-day-old rats were cultured for 1, 3, and 5 days in medium containing antisense oligodeoxynucleotide (AS-ODN) for IGF-I. Real-time RT-PCR analysis showed that the levels of IGF-I and IGF binding protein (IGFBP) 3 mRNAs in the AS-ODN group were significantly decreased. After 3 days' culture, the number of necrotic cells was observed in the undifferentiated mesenchymal cell layer. These cells were TUNEL-positive and confirmed to be apoptotic by electron microscopic observation. Immunoblotting revealed that expression of cleaved caspase3 was increased with AS-ODN. These results may suggest that the cells in the undifferentiated mesenchymal cell layer of the mandibular condyle require IGF-I for survival.