A seric low molecular weight factor modulates IGFs effects on chick cartilage metabolism.

The effects of recombinant human insulin-like growth factors (rhIGF-I and rhIGF-II) alone and in combination with a partially purified serum low molecular weight growth factor (LMW-GF) were studied by measuring proteoglycan (PG) and total protein synthesis by chick embryo cartilage. rhIGF-I alone did not increase the incorporation of L[3H]serine or [35S]Na2SO4 into whole cartilages. LMW-GF + rhIGF-I markedly increased the incorporation of these precursors. rhIGF-I alone stimulated D[3H]glucosamine uptake, and LMW-GF increased the effect of rhIGF-I. These results for whole cartilage were reproduced with glycosaminoglycans (GAG) extracted from cartilage. LMW-GF acted in synergy with rhIGF-I to stimulate PG core protein synthesis, xylosyl transferase activity and sulfation. Total protein synthesis, as measured by [35S]methionine uptake, was not altered by rhIGF-I. LMW-GF plus rhIGF-I increased the incorporation of this precursor into whole cartilage. The effect of rhIGF-II on PG synthesis was different from that of rhIGF-I. rhIGF-II alone stimulated GAG chain lengthening and sulfation. LMW-GF did not modify the effect of rhIGF-II on these steps. In contrast, rhIGF-II did not stimulate the synthesis of core protein. LMW-GF plus rhIGF-II increased the [3H]serine incorporation into the whole cartilage, but this combination did not stimulate the uptake of [3H]serine into extracted GAG. rhIGF-II plus LMW-GF were also without effect on xylosyl transferase activity. The combination of these factors increased the [35S]methionine incorporation into cartilage total proteins. These results suggest that rhIGF-II does not regulate the PG core protein synthesis, but in combination with LMW-GF, stimulates the synthesis of proteins other than proteoglycan core protein.