In vitro effect of multiplication stimulating activity (MSA) on human fetal and postnatal cartilage.

Although insulin-like growth factors may have a physiological role in fetal growth, little is known of their biological action on human fetal tissues. In the present study, the action of multiplication stimulating activity (MSA) on human fetal cartilage in vitro, has been examined and compared with its effect on postnatal cartilage. Addition of MSA (10-100 ng/ml) resulted in a dose dependent increase in [3H]thymidine incorporation into fetal cartilage aged between 15 and 18 weeks of gestation. The mean response with 100 ng/ml was 143 +/- 18% (n = 10) of basal levels. The increase in [35S]sulphate incorporation was variable, the mean (131 +/- 36%, n = 5) being not significantly greater than in controls. The increase in [3H]thymidine incorporation on addition of MSA was not seen in fetal cartilage of earlier (13/14 wk) or later (19 wk) gestational age. MSA-III (a highly purified component of MSA) at 100 ng/ml increased [3H]thymidine and [35S]sulphate incorporation into cartilage from a fetus of 17 weeks to 165% and 150%, respectively, but had no effect on the incorporation of either isotope into cartilage from a fetus of 19 weeks gestation. In contrast to the mitogenic effects of MSA on fetal cartilage, the same preparation had no effect on either [3H]thymidine or [35S]sulphate incorporation into postnatal cartilage. These results may reflect developmental changes in cartilage response to insulin-like growth factors similar to those reported in human brain.