A local bone anabolic effect of rhFGF2-impregnated gelatin hydrogel by promoting cell proliferation and coordinating osteoblastic differentiation
A local bone anabolic effect of rhFGF2-impregnated gelatin hydrogel by promoting cell proliferation and coordinating osteoblastic differentiation
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DOI：
10.1016/j.bone.2008.12.017
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发表时间：
2009-04-01
期刊：
影响因子：
4.1
通讯作者：
Takagi, Ritsuo
中科院分区：
文献类型：
--
作者：
Kodama, Naoki;Nagata, Masaki;Takagi, Ritsuo
rhFGF 2的骨合成代谢作用是通过激活成骨细胞的增殖和分化实现的。Runx 2和Bmp 2的伴随上调意味着FGF/FGFR信号传导对成骨细胞分化的协调功能。简介：生长因子暴露的持续时间和组织浓度在组织再生中是重要的。本研究分析了rhFGF 2的可用性。使用缓释明胶水凝胶系统。为了研究骨合成代谢效应的生物学方面，我们进行了形态学和细胞增殖测定，以及使用体内定位和定量程序的成骨细胞相关基因的基因表达分析。20 μ g rhFGF-2明胶水凝胶植入诱导骨形成的实验研究应用显微CT、增殖细胞核抗原（PCNA）免疫组化、原位杂交和定量真实的时间聚合酶链反应结合激光显微切割技术，对重组人成纤维细胞生长因子2（+）（rhFGF 2（+））在小鼠上颌骨上的表达进行分析结果：rhFGF 2（+）明胶凝胶植入后，骨性上颌骨体积增加到原来的1.58倍（p = 0.002）。在分化的成骨细胞和未分化的间充质细胞中观察到PCNA阳性细胞核的数量增加。Fgfr 1、Fgfr 2和Runx 2主要在分化的成骨细胞中共表达，但也在成骨细胞标志物阴性的梭形细胞中共表达，这些细胞分散在增生骨膜的外层内。LMD-QPCR结果显示，rhFGF 2缓释后Bmp 2表达上调，同时Fgfr 1、Fgfr 2和Runx 2的转录增加。结论：rhFGF 2缓释可促进成骨细胞的增殖和分化，从而促进上颌骨骨形成。这表明FGF/FGFR信号通过同时激活RUNX 2和BMP 2途径来协调骨合成代谢作用。明胶水凝胶系统能够使rhFGF 2在组织中持续缓慢释放，具有优化骨再生的优点。(C)2008年爱思唯尔公司All rights reserved.
The bone anabolic effect of rhFGF2 is attributed to activation of proliferation and differentiation of osteoblasts. Concomitant up-regulation of Runx2 and Bmp2 implies a coordinative function of FGF/FGFR signaling on osteoblast differentiation.Introduction: Duration and tissue concentration of growth factor exposure are important in tissue regeneration. This Study analyzed the availability of rhFGF2. using a sustained release gelatin hydrogel system. To examine biological aspects of the bone anabolic effect, we carried Out morphological and cell proliferation assays together with gene expression analyses of osteoblast related genes induced by rhFGF2 using localizing and quantifying procedures in vivo.Materials and methods: Bone formation induced by implantation of gelatin hydrogel impregnated with 20 mu g rhFGF2 (rhFGF2(+)) onto mice maxillae was analyzed by micro Computed tomography, proliferating cell nuclear antigen (PCNA) immunohistochemistry, in situ hybridization and quantitative real time polymerase chain reaction combined with laser microdissection (LMD-QPCR).Results: The bony maxilla was augmented to 1.58 times its original Volume (p = 0.002) by the implantation of rhFGF2(+) gelatin hydrogel. An increased number of PCNA-positive nuclei were observed among differentiated osteoblasts as well as undifferentiated mesenchymal cells. Fgfr1, Fgfr2 and Runx2 were shown to be co-expressed mainly in differentiated osteoblasts but also in osteoblast marker negative spindle-shaped cells that were scattered within the Outer layer of hyperplastic periosteum. LMD-QPCR revealed up-regulation of Bmp2 expression accompanied by increased transcription of Fgfr1, Fgfr2 and Runx2 by rhFGF2 controlled release.Conclusions: rhFGF2 sustained release results in bone formation oil the maxilla by positively regulating the expansion and differentiation of osteoblastic cells. It is suggested that FGF/FGFR signaling coordinates a bone anabolic effect by Simultaneously activating RUNX2 and BMP2 pathways. The gelatin hydrogel system, which enables a sustained slow rate of release of rhFGF2 ill tissue has advantages of optimizing bone regeneration. (C) 2008 Elsevier Inc. All rights reserved.