Effects of recombinant human fibroblast growth factor-2 on osteogenic cell populations during orthopic osteogenesis in vivo

Abstract

The osteogenic effects of fibroblast growth factor-2 (FGF-2) in vivo on different cell populations of the osteoblastic cell lineage have not been fully elucidated. In this study, the efficacy of recombinant human fibroblast growth factor-2 (rhFGF-2) to stimulate orthopic bone formation in transosseous rat mandibular defects, with different cell populations allowed access to the defects, was investigated with the aim to further decipher FGF-2 effects. Three different doses of rhFGF-2 (10 ng, 100 ng, and 1 μg) were delivered in an absorbable collagen sponge carrier, whereas some defects were implanted with the carrier only, and some were left untreated. Barrier membranes, made of microporous expanded polytetrafluoroethylene, were simultaneously placed over half the number of defects in each treatment group, thus forcing osteogenic cells to be derived from intraosseous sources. Evaluation was made by light microscopy and computerized image analysis after 12 and 24 of days healing. Whereas no general stimulatory effect could be ascertained at 12 days, higher rhFGF-2 doses decreased bone formation by both intraosseously and periosteally derived cells. At 24 days, a clear, although rather limited, stimulatory effect on osteogenesis was observed, but again a decrease was observed with the 1 μg dose. At both observation periods, an increased number of osteocytes was found in the newly formed bone at sites treated with the lower rhFGF-2 doses, whereas the high-dose rhFGF-2 resulted in a return to control levels, irrespective of whether cells were intraosseously derived or from the periosteum also. Based on differential analysis of bone healing by cells from different sources as well as on bone cellularity, the results suggest that rhFGF-2 in vivo exerts a stimulatory effect on proliferation of committed osteoblastic cells. This effect is biphasic, in that higher doses are without effect or may even be inhibitory. No inductive effect on osteoblast recruitment could be found. These effects differ from those of, for instance, BMP-2 and TGF-β1.