Cooperation of synthetic insulin-like growth factor I/somatomedin C and 1,25-dihydroxyvitamin D 3 on regulation of function in clonal osteoblastic cells

Abstract

We investigated the effects of insulin-like growth factor I/somatomedin C (IGF-I/SM-C), and the interaction of IGF-I and 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3) on mouse clonal osteoblasts, MC3T3-E1. IGF-I stimulated [ 3H]thymidine incorporation into the DNA of the cells at concentrations of 1.3 −130 × 10 −9. The alkaline phosphatase (ALP) activity in cultures was also raised by the hormone at the same concentrations. The optimal dose of IGF-I was 13 × 10 −9 M. Co-addition of IGF-I (1.3 −130 × 10 −9 M) and 1,25(OH) 2D 3 (10 −11 to 10 −10 M) to the culture of MC3T3-E1 cells caused a synergistic increase in ALP activity. 25(OH)D 3 and 24,25(OH) 2D 3 showed a similar effect with IGF-I at 1000–2000 times higher concentrations than 1,25(OH) 2D 3. [ 3H]Proline incorporation into collagenase digestible protein (CDP) in media was stimulated dose-dependently by 1GF-I up to 2.2-fold over the control levels at 130 × 10 −9 M. Addition of 1,25(OH) 2D 3 (5 × 10 −11 M) and IGF-I further elevated the proline incorporation into CDP. However, the increment in CDP synthesis, induced by the two hormones was less than the increment in ALP activity. Thus, we conclude (1) that IGF-I stimulates both cell replication and differentiated functions in cultured murine osteoblasts and (2) that IGF-I and 1,25(OH) 2D 3 have the synergistic effect on ALP activity and the additive effect on collagen synthesis in MC3T3-E1 cells.