EFFECTS AND FATE OF HUMAN IGF-BINDING PROTEIN-5 IN RAT OSTEOBLAST CULTURES

Osteoblasts prepared from calvaria of newborn rats produce insulin-lik e growth factors (IGF) and IGF-binding proteins (IGFBP). IGFBP-5 was d iscovered in bone extracts. However, we could not detect IGFBP-5 in th e medium of newborn rat osteoblasts, although we found mRNA expression . To find an explanation for this discrepancy and to learn more about the physiological role of IGFBP-5 in these cells, we studied the biolo gical activity and the fate of recombinant human (rh) IGFBP-5 in compa rison to rhIGFBP-3. IGFBP-5 but not IGFBP-3 stimulated thymidine incor poration into DNA both in the absence and presence of IGF-I. However, IGFBP-5 did not enhance uridine incorporation into RNA and glucose inc orporation into glycogen. I-125-rhIGFBP-5 but not I-125-rhIGFBP-3 rapi dly disappeared from the culture medium consistent with the observatio n that endogenous (rat) IGFBP-5 but not IGFBP-5 accumulated in the med ium. However, intact I-125-labeled or unlabeled rhIGFBP-5 was associat ed with the cell-layer matrix, whereas IGFBP-5 fragments appeared in t he medium. Trapping of IGFBP-5 in the cell layer matrix may enhance lo cal availability of IGF.