Local effects of transforming growth factor-β1 on rat calvaria:: Changes depending on the dose and the injection site

Transforming growth factor-beta(1), (TGF-beta(1)) has opposite effects on osteoblastic cells in vitro, namely an inhibitory or stimulatory effect on cell differentiation. Because these effects are dependent on TGF-beta(1), concentration or culture condition, we investigated whether the in vivo effects of TGF-beta(1) on bone formation in infant rat calvaria were affected by the dose or the injection site. Human platelet-derived TGF-beta(1) was injected subcutaneously onto the periosteal surface of parietal bone of 4-week-old rats at doses of 5 or 20 ng/100 mu l per animal for 14 days, and the local effect on bone formation was examined by bone histomorphometry. TGF-beta(1), treatment for 7 days decreased the mineral apposition rate, bone formation rate, and elongated mineralization lag time at the injection site. This change became more prominent when treatment continued for 14 days. These changes were restricted to the TGF-beta(1)-exposed area. Multiple subcutaneous injections of a relatively high dose (200ng/100 mu l per animal) of TGF-beta(1), induced woven bone formation, in addition to marked inhibition of bone formation rate and prolongation of mineralization lag time. On the other hand, direct exposure of TGF-beta(1) in the subperiosteal layer induced woven bone with periosteal cell proliferation even at a single injection of a low dose (5 or 50 ng/25 mu l) of TGF-beta(1). In conclusion, the in vivo effects of TGF-beta(1) on bone formation varied depending on its concentration and injection site. Also, subcutaneous injection of relatively low doses of TGF-beta(1), inhibited local lamellar bone formation.