B. Gabbitas et E. Canalis, INSULIN-LIKE GROWTH-FACTORS SUSTAIN INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-5 EXPRESSION IN OSTEOBLASTS, American journal of physiology: endocrinology and metabolism, 38(2), 1998, pp. 222-228
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.