Am. Delany et al., AUTOCRINE DOWN-REGULATION OF COLLAGENASE-3 IN RAT BONE CELL-CULTURES BY INSULIN-LIKE GROWTH-FACTORS, Endocrinology, 137(11), 1996, pp. 4665-4670
Insulin-like growth factors (IGF)-I and -II are presumed to act as aut
ocrine regulators of bone formation. Recently, we demonstrated that IG
F-I and -II inhibit bone collagen degradation and collagenase-3 synthe
sis in osteoblast cultures. Therefore, we tested the autocrine role of
IGFs in the endogenous expression of collagenase-3 in cultures of ost
eoblast-enriched cells from 22-day fetal rat calvariae (Ob cells). Ste
ady-state messenger RNA (mRNA) levels were determined by Northern blot
analysis and collagenase concentrations in the culture medium were de
termined by Western immunoblot. Basal level collagenase-3 transcripts
decreased in Ob cell cultures, coinciding with an increase in IGF-I an
d -II protein levels. Removal of the conditioned medium modestly incre
ased collagenase-3 mRNA levels and restored the ability of exogenously
added IGF-I to repress collagenase-3 transcripts. IGF neutralizing an
tibodies and IGF binding proteins-2 and -3 in excess increased and sus
tained collagenase mRNA, heterogeneous nuclear RNA, and protease level
s in Ob cell cultures. In conclusion, IGF-I and -II are autocrine repr
essors of collagenase-3 synthesis, and this effect may contribute to t
heir actions on the maintenance of a normal bone collagen matrix.