Regulation of Bone Collagen Synthesis by Insulin

Both clinical and laboratory studies have reported a stimulation of bone collagen synthesis by insulin. However, the mechanisms of regulation of collagen synthesis have not been determined. Towards this objective, we have measured and correlated rates of collagen protein synthesis and steady state levels of type I procollagen xnRNA in the osteoblast enriched central bone of cultured 21 day fetal rat calvaria. Over 95% of the total collagens synthesized by central bone were type I collagen. The stimulation of both collagen synthesis and type I procollagen mRNA was dose dependent over the culture range of 0.3 to 100 nM insulin and a two-fold increase over control cultures was seen after 24h of culture with 3 nM insulin. The increase in collagen synthesis was initially detected 12-18h after the addition of 3nM insulin. Levels of pro al(I) and pro a2(I) mRNA, elevated as early as 3h after insulin addition, continued to accumulate over the 24h culture period. The removal of insulin from calvaria cultured for 24h with 3nM insulin caused rates of collagen synthesis to return to control 5h after insulin deprivation while pro al(I) mRNA decreased to control by 3h of insulin deprivation. These data suggest that alterations in collagen synthesis are preceded by alterations in procollagen mRNA levels and that insulin may, in part, regulate collagen synthesis by changing steady state levels of procollagen RNA.