Regulatory Effects of Insulin-Like Growth Factors I and II on Bone Collagen Synthesis in Rat Calvarial Cultures*

Insulin-like growth factors I and II (IGF-I and -II) are polypeptides secreted by skeletal cells and are considered regulators of bone formation. IGF-I and -II were studied for their effects on collagen synthesis and degradation in cultures of intact fetal rat calvariae and on type I collagen transcript levels in osteoblast-enriched (Ob) cells from fetal rat parietal bone. IGF-I and -II increased [3H]proline incorporation into type I collagen independently of their effect on cell replication. IGF-I and -II also decreased collagen degradation in calvarial cultures. Both factors had similar actions, although IGF-I stimulated collagen synthesis at 10 nM, and IGF-II at 30 nM. In Ob cells, IGF-I and -II also increased [3H]proline incorporation into type I collagen, but the effect was seen at 100 nM, and neither factor decreased collagen degradation. Slot blot analysis of IGF-I- and IGF-II-treated cells, using a rat type I collagen cDNA probe, revealed an increase in type I collagen transcripts. In conclusion, IGF-I and -II increase bone collagen synthesis and decrease collagen degradation in cultures of intact calvariae; the effect on collagen synthesis correlates with an increase in transcript levels in Ob cells.