Effect of recombinant human fibroblast growth factor-2 on intramuscular ectopic osteoinduction by recombinant human bone morphogenetic protein-2 in rats

To clarify the effects of recombinant human fibroblast growth factor-2 (rhFGF-2) on the osteoconduction ability of recombinant human bone morphogenetic protein-2 (rhBMP-2) in vivo, rhBMP-2 (2 microg) was mixed with different doses of rhFGF-2 (0, 16, 80, 400, or 2,000 ng), and implanted into the lower leg muscle of rats using type I collagen as a carrier. Twenty-one days later, ectopic neoplastic bones had bone mineral content, bone area, and bone mineral density measured by means of dual energy X-ray absorptiometry and imaged by soft X-ray. The values for alkaline phosphatase activity and calcium content were determined, and histology obtained. In the group treated with rhFGF-2 at 16 ng, alkaline phosphatase activity, calcium content, bone mineral content, bone area, and bone mineral density were the greatest of all treatment groups, and the richest trabeculae were histologically observed in this group. In the groups treated with rhFGF-2 at 80, 400, or 2,000 ng, bone formation was suppressed in a dose-dependent manner. These results indicate that rhFGF-2 promotes ectopic rhBMP-2-related osteoinduction at a low concentration (16 ng) in vivo, and that it suppresses osteoinduction at a higher amount (>80 ng).