STIMULATION OF ENDOSTEAL BONE-FORMATION BY SYSTEMIC INJECTIONS OF RECOMBINANT BASIC FIBROBLAST GROWTH-FACTOR IN RATS

In vivo effects of basic fibroblast growth factor (bFGF) on bone forma tion was examined in rats. Daily systemic injections of 100 mu g/kg bF GF for 7 days caused a marked stimulation of endosteal bone formation in both cortical and secondary cancellous bone areas. Histological exa minations revealed that the sequence of responses to the injections of bFGF consisted of three phases: an early increase in the number of pr eosteoblastic cells over the osteoblastic cell layer (days 1-3), recru itment of osteoblasts from preosteoblastic cells (days 3-5), and an in crease in new bone formation (days 5-7). These histological changes in the endosteum correlated closely with histomorphometrical parameters of bone formation, and the endosteal mineral apposition rate was almos t unaffected during the initial 4 days but was markedly enhanced after this period. Immunohistochemical examinations using antitransforming growth factor (TGF)-beta 1 antibody demonstrated that immunostaining o f preosteoblastic cells for TGF-beta already increased 1 day after bFG F treatment. Distribution of TGF-beta in osteoblasts and bone matrices began to increase on day 3, and all the osteoblasts and new bone matr ices were intensively immunostained on day 7. These results demonstrat e that systemic injections of bFGF in rats stimulate endosteal bone fo rmation, and that the stimulation of bone formation is preceded by an initial increase in preosteoblastic cells with later recruitment of os teoblasts from these cells. Because the distribution of TGF-beta in th e endosteal cells is increased by bFGF, the effect of bFGF may at leas t in part be mediated by TGF-beta. However, the precise mechanism of a ction of bFGF on bone formation remains to be clarified.