Abstract
Somatomedin C/insulin-like growth factor I the major regulator of cartilage growth and (GAG) biosynthesis. We have previously shown of sulfate incorporation into GAG by SM is dependent upon protein synthesis, particularly synthesis of GAG protein core. Using a cultured chick chondrocyte system, we investigated the time necessary for stimulation by SM. Increased incorporation of thymidine into DNA occurred after a lag of 5 hours, sulfate into GAG after 1-2 hours, and leucine into protein and uridine into RNA within 15 minutes. Because stimulation of RNA and protein synthesis are both rapid, we studied whether the stimulation of GAG biosynthesis requires SM stimulation of RNA. Actinomycin D (5 ug/ml, which inhibits RNA synthesis without blocking SM stimulation of native GAG synthesis) and 4-methyl-umbelliferyl-B-D-xyloside (1 mM, which acts as an acceptor for initiation of GAG chains) were used for these studies. Addition of xyloside increased incorporation of sulfate into soluble GAG, but decreased incorporation into cell-bound GAG. The effect of SM was still present after addition of the xyloside with and without actinomycin D. We conclude that SM stimulation of protein and RNA synthesis occurs within minutes after addition of SM, and before stimulation of sulfation or DNA synthesis. This stimulation is independent of RNA synthesis, and is reflected by an increase in xyloside-initiated chains.
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Kemp, S., Frindik, J., Ma, FJ. et al. 1218 SITES OF ACTION OF SOMATOMEDIN ON CHICK CHONDROCYTES. Pediatr Res 19, 313 (1985). https://doi.org/10.1203/00006450-198504000-01248
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DOI: https://doi.org/10.1203/00006450-198504000-01248