A SERIC LOW-MOLECULAR-WEIGHT FACTOR MODULATES IGFS EFFECTS ON CHICK CARTILAGE METABOLISM

The effects of recombinant human insulin-like growth factors (rhlGF-I and rhlGF-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 cartila ge. rhlGF-I alone did not increase the incorporation of L[H-3]serine o r [[S-35]]Na2SO4 into whole cartilages. LMW-GF + rhlGF-I markedly incr eased the incorporation of these precursors, rhlGF-I alone stimulated D[H-3]glucosamine uptake, and LMW-GF increased the effect of rhlGF-I. These results for whole cartilage were reproduced with glycosaminoglyc ans (GAG) extracted from cartilage. LMW-GF acted in synergy with rhlGF -I to stimulate PG core protein synthesis, xylosyl transferase activit y and sulfation. Total protein synthesis, as measured by [S-35]methion ine uptake, was not altered by rhlGF-I. LMW-GF plus rhlGF-I increased the incorporation of this precursor into whole cartilage. The effect o f rhlGF-II on PG synthesis was different from that of rhlGF-I. rhlGF-I I alone stimulated GAG chain lengthening and sulfation. LMW-GF did not modify the effect of rhlGF-II on these steps. In contrast, rhlGF-II d id not stimulate the synthesis of core protein. LMW-GF plus rhlGF-II i ncreased the [H-3]serine incorporation into the whole cartilage, but t his combination did not stimulate the uptake of [H-3]serine into extra cted GAG. rhlGF-II plus LMW-GF were also without effect on xylosyl tra nsferase activity. The combination of these factors increased the [S-3 5]methionine incorporation into cartilage total proteins. These result s suggest that rhlGF-II does not regulate the PG core protein synthesi s, but in combination with L-MW-GF, stimulates the synthesis of protei ns other than proteoglycan core protein.