Fibroblast growth factor-2 augments recombinant human bone morphogenetic protein-2-induced osteoinductive activity
Fibroblast growth factor-2 augments recombinant human bone morphogenetic protein-2-induced osteoinductive activity
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DOI：
10.1007/s10439-006-9092-x
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发表时间：
2006-05-01
影响因子：
3.8
通讯作者：
Tanne, Kazuo
中科院分区：
文献类型：
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作者：
Tanaka, Eiji;Ishino, Yoshihiro;Tanne, Kazuo
重组人BMP-2 （rhBMP-2）诱导的成骨活性随着受体年龄的增长成比例地减弱。为了弥补这种钝性，已考虑使用成纤维细胞生长因子-2 （FGF-2）。本研究的目的是确定FGF-2是否能增强rhBMP-2引起的骨诱导活性，并评估衰老对rhBMP-2和FGF-2共同给药诱导的骨形成的影响。64只8周龄Wistar雄性大鼠（青春期前）和16周龄Wistar雄性大鼠（青春期后）分别在双侧顶骨处植入骨缺损，并采用聚乳酸-聚乙醇酸共聚物/明胶海绵（PGS），分别浸没rhBMP-2 + 0 ng、25 ng和250 ng FGF-2 （n=10）。在移植后2周，rhBMP-2+FGF-2组的新骨体积似乎比单独rhBMP-2组大。4周时，新骨形成与相邻的原骨连接。在青春期前的大鼠中，所有新形成的骨头都类似地钙化。在青春期后的大鼠中，只有rhBMP-2+25 ng FGF-2组显示出这种更高程度的钙化。2周时，rhBMP-2+25 ng FGF-2组大鼠碱性磷酸酶（ALP）活性均显著高于青春期前和青春期后的rhBMP-2组（p < 0.05）。结果表明，低剂量FGF-2可增强rhBMP-2移植部位的钙化程度和ALP活性，特别是在青春期后的大鼠中。因此，FGF-2将是补偿rhBMP-2随着衰老而降低的骨诱导活性的候选物。
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.