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Fibroblast Growth Factor-2 Augments Recombinant Human Bone Morphogenetic Protein-2-Induced Osteoinductive Activity

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Abstract

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.

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Authors and Affiliations

  1. Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan

    Eiji Tanaka, Yoshihiro Ishino, Akiko Sasaki, Takuro Hasegawa, Mineo Watanabe, Diego A. Dalla-Bona, Eizo Yamano, Theo M. G. J. van Eijden & Kazuo Tanne

  2. Department of Functional Anatomy, ACTA, Amsterdam, The Netherlands

    Theo M. G. J. van Eijden

  3. Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan

    Eiji Tanaka

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  1. Eiji Tanaka
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Tanaka, E., Ishino, Y., Sasaki, A. et al. Fibroblast Growth Factor-2 Augments Recombinant Human Bone Morphogenetic Protein-2-Induced Osteoinductive Activity. Ann Biomed Eng 34, 717–725 (2006). https://doi.org/10.1007/s10439-006-9092-x

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  • DOI: https://doi.org/10.1007/s10439-006-9092-x

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