Stimulatory effects of basic fibroblast growth factor and bone morphogenetic protein-2 on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells
Stimulatory effects of basic fibroblast growth factor and bone morphogenetic protein-2 on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells
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DOI：
10.1359/jbmr.1997.12.10.1606
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发表时间：
1997-10-01
影响因子：
6.2
通讯作者：
Caplan, AI
中科院分区：
文献类型：
--
作者：
Hanada, K;Dennis, JE;Caplan, AI
骨髓基质中含有多能间充质祖细胞，可分化为成骨细胞;我们将这些细胞称为间充质干细胞（MSC），碱性成纤维细胞生长因子（bFGF）和骨形态发生蛋白-2（BMP-2）分别由于它们的促有丝分裂和分化活性而参与成骨调节过程，本研究探讨并比较bFGF和BMP-2对地塞米松（Dex）依赖的大鼠骨髓间充质干细胞体外成骨分化的影响。bFGF暴露6天显著刺激细胞生长并诱导成骨细胞分化，如通过骨钙素mRNA表达（第14天）、骨结节形成（第18天）和钙沉积（第18天）所示。这些结果表明bFGF增强了Dex处理的骨髓MSC的促有丝分裂活性和成骨发育。相反，BMP-2没有像bFGF那样强烈地诱导成骨。与对照相比，暴露于BMP-2略微增加了骨结节数量和钙含量。早在第11天，MSC暴露于BMP-2和bFGF诱导了骨钙素mRNA的表达和矿化骨样结节，并导致骨形成的增强比单独的任一因子更显著。与这些结果一致，植入体内的多孔磷酸钙陶瓷立方体，这些数据表明，bFGF和BMP-2的联合处理协同增强了bFGF在大鼠骨髓MSC培养物中的成骨能力。
Bone marrow stroma contains multipotential mesenchymal progenitor cells which can differentiate into osteoblastic cells; we refer to these cells as mesenchymal stem cells (MSCs), Basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) have been implicated in the osteogenic regulatory process by virtue of their mitogenic and differentiation activities, respectively, This study examines and compares the effects of bFGF and BMP-2 on dexamethasone (Dex)-dependent in vitro osteogenic differentiation of rat marrow-derived MSCs. A 6-day exposure to bFGF markedly stimulated cell growth and induced osteoblastic differentiation as shown by osteocalcin mRNA expression (day 14), bone nodule formation (day 18), and calcium deposition (day 18), These results indicate that bFGF enhances both mitogenic activity and osteogenic development of Dex-treated marrow MSCs, In contrast, BMP-2 did not induce osteogenesis as strongly as bFGF, Thus, exposure to BMP-2 slightly increased bone nodule number and calcium content compared,vith the control, Exposure of MSCs to both BMP-2 and bFGF induced expression of osteocalcin mRNA and mineralizing bone-like nodules as early as day 11 and resulted in enhancement of bone formation more markedly than either factor alone, Consistent with these results, porous calcium phosphate ceramic cubes implanted in vivo, which were loaded with MSCs pre-exposed to both bFGF and BMP-2, showed higher histologic score for bone formation than those with MSCs pre-exposed to either bFGF or BMP-2 alone, These data indicate that combined treatment with bFGF and BMP-2 synergistically enhances the osteogenic potency of bFGF in rat marrow MSC culture.