Fibroblast growth factor-2 augments recombinant human bone morphogenetic protein-2-induced osteoinductive activity

• Published in: Annals of biomedical engineering Vol. 34; no. 5; pp. 717 - 725
• Main Authors: Tanaka, Eiji, Ishino, Yoshihiro, Sasaki, Akiko, Hasegawa, Takuro, Watanabe, Mineo, Dalla-Bona, Diego A, Yamano, Eizo, van Eijden, Theo M G J, Tanne, Kazuo
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.05.2006
• Subjects: Aging; Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins - administration & dosage; Bone Morphogenetic Proteins - genetics; Bone Transplantation - methods; Bones; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Fibroblast Growth Factor 2 - administration & dosage; Humans; Male; Osteogenesis - drug effects; Osteogenesis - physiology; Polylactic acid; Rats; Rats, Wistar; Recombinant Proteins - administration & dosage; Rodents; Skull Fractures - pathology; Skull Fractures - surgery; Transforming Growth Factor beta - administration & dosage; Transforming Growth Factor beta - genetics
• ISSN: 0090-6964; 1573-9686
• DOI: 10.1007/s10439-006-9092-x

The osteoinductive activity induced by recombinant human BMP-2 (rhBMP-2) blunts proportionately as the recipient ages. In order to compensate for this bluntness administration of fibroblast growth factor-2 (FGF-2) has been considered. The aim of this study was to determine whether FGF-2 administration augments osteoinductive activity caused by rhBMP-2 and to evaluate the effect of aging on bone formation induced by coadministration of rhBMP-2 and FGF-2. Sixty-four Wistar strain male rats of 8-week-old (prepubertal) and 16-week-old (postpubertal) received bone defects bilaterally in the parietal bone and the defects were filled by a polylactic acid polyglycolic acid copolymer/gelatin sponge (PGS) impregnated with rhBMP-2 plus 0 ng, 25 ng, and 250 ng FGF-2 (n=10 in each). At 2 weeks after grafting, the new bone volume seemed to be larger in the rhBMP-2+FGF-2 groups than in the rhBMP-2 alone group. At 4 weeks, the new bone formation was linked to the adjacent original bone. In the prepubertal rats, all newly formed bone was similarly calcified. In the postpubertal rats, only the rhBMP-2+25 ng FGF-2 group showed this higher degree of calcification. At 2 weeks, alkaline phosphatase (ALP) activity in the rhBMP-2+25 ng FGF-2 group was significantly (p<0.05) larger than that in the rhBMP-2 group in both prepubertal and postpubertal rats. This result shows that low-dose administration of FGF-2 enhanced the degree of calcification and ALP activity in the rhBMP-2 grafting site especially in the postpubertal rats. Therefore, FGF-2 would be a candidate to compensate for the reduction of osteoinductive activity of rhBMP-2 with aging.