INSULIN-LIKE GROWTH-FACTORS SUSTAIN INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-5 EXPRESSION IN OSTEOBLASTS

Insulin-like growth factors (IGFs)I and II are considered to be autocr ine regulators of bone cell function. Recently, we demonstrated that I GF-I induces IGF-binding protein-5 (IGFBP-5) expression in cultures of osteoblast-enriched cells from 22-day fetal rat calvariae (Ob cells). In the present study, we postulated that IC;Fs play an autocrine role in the maintenance of IGFBP-5 basal expression in Ob cells. IGFBP-2 a nd -3, at concentrations that bind endogenous IGFs, decreased IGFBP-5 mRNA levels, as determined by Northern blot analysis, and protein leve ls, as determined by Western immunoblots of extracellular matrix extra cts of Ob cells. IGFBP-8 and -3 in excess inhibited IGFBP-5 heterogene ous nuclear RNA levels, as determined by RT-PCR, and did not alter the half-life of IGFBP-5 mRNA in transcriptionally arrested Ob cells. In conclusion, blocking endogenous IGFs in Ob cells represses IGFBP-5 exp ression, suggesting that IGFs are autocrine inducers of IGFBP-5 synthe sis in osteoblasts.