Similar effects of recombinant human insulin-like growth factor-I and II on cellular activities in flexor tendons of young rabbits: experimental studies in vitro.

Abstract

To improve the understanding of factors with the potential of affecting the healing of flexor tendons, this study compared the cellular effects of recombinant human insulin-like growth factor-II with those of recombinant human insulin-like growth factor-I in matched pairs of deep flexor tendons of young rabbits. Dose-response effects on the synthesis of DNA and matrix proteins of either factor alone or in combination were investigated in short-term culture, and effects on synthesis and turnover of matrix components were compared in long-term culture. Both factors stimulated proteoglycan, collagen, noncollagen protein, and DNA synthesis in a dose-dependent manner in the range of 10-500 ng/ml. Insulin-like growth factor-I increased proteoglycan synthesis to as much as six times that of controls but was less potent than insulin-like growth factor-II. Both factors stimulated increased cell proliferation by as much as five times compared with control values, but insulin-like growth factor-I was more potent than insulin-like growth factor-II. The two factors in combination did not enhance the synthesis of matrix proteins and DNA as compared with either factor alone. Insulin-like growth factor-I counteracted the decrease in collagen synthesis and stimulated protein synthesis to a higher degree than insulin-like growth factor-II in long-term culture. Both factors had similar effects on matrix turnover, with estimated half times (t1/2) for elimination of newly labeled proteoglycans and proteins of 11 and 8 days, respectively. Insulin-like growth factor-II is capable of stimulating cell proliferation and matrix metabolism in tendon explants of young rabbits at levels similar to those of insulin-like growth factor-I; in combination, the two growth factors are unable to augment the stimulatory effects of either of the factors alone.