Stromal derived factor-1 regulates bone morphogenetic protein 2-induced osteogenic differentiation of primary mesenchymal stem cells.
Stromal derived factor-1 regulates bone morphogenetic protein 2-induced osteogenic differentiation of primary mesenchymal stem cells.
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DOI：
10.1016/j.biocel.2010.03.020
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发表时间：
2010-07
影响因子：
4
通讯作者：
Zhu, Wei
中科院分区：
文献类型：
--
作者：
Hosogane, Naobumi;Huang, Zhiping;Rawlins, Bernard A.;Liu, Xia;Boachie-Adjei, Oheneba;Boskey, Adele L.;Zhu, Wei
关键词：
基质衍生因子-1（SDF-1）是一种趋化因子信号分子，与其跨膜受体CXC趋化因子受体-4（CXCR 4）结合。虽然我们以前检测到SDF-1与骨形态发生蛋白2（BMP 2）共同需要间充质C2 C12细胞分化为成骨细胞，但尚不清楚SDF-1是否类似地参与间充质干细胞（MSC）的成骨分化。因此，在这里，我们研究了SDF-1信号转导在BMP 2诱导的人和小鼠骨髓来源的原代MSC成骨分化过程中的作用。我们的数据显示，阻断SDF-1/CXCR 4信号轴或向MSC中加入SDF-1蛋白显著影响BMP 2诱导的碱性磷酸酶（ALP）活性和骨钙素（OCN）合成，分别是前成骨细胞和成熟成骨细胞的标志物。此外，在MSC的终末分化过程中，破坏SDF-1信号传导损害骨结节矿化。此外，我们检测到，SDF-1信号传导的阻断抑制BMP 2诱导的Runt相关因子-2（Runx 2）和osterix（Osx）的早期表达，这两个“主”成骨调节因子，SDF-1的作用是通过细胞内Smad和Erk激活介导的。总之，我们的研究结果表明SDF-1在BMP 2诱导的MSC成骨分化中的调节作用，因为干扰SDF-1信号传导影响MSC响应BMP 2刺激向成骨细胞的分化。这些数据为MSC成骨的分子机制提供了新的见解，并将有助于MSC治疗在广泛的骨科情况下增强骨形成和再生的发展。
Stromal derived factor-1 (SDF-1) is a chemokine signaling molecule that binds to its transmembrane receptor CXC chemokine receptor-4 (CXCR4). While we previously detected that SDF-1 was co-required with bone morphogenetic protein 2 (BMP2) for differentiating mesenchymal C2C12 cells into osteoblastic cells, it is unknown whether SDF-1 is similarly involved in the osteogenic differentiation of mesenchymal stem cells (MSCs). Therefore, here we examined the role of SDF-1 signaling during BMP2-induced osteogenic differentiation of primary MSCs that were derived from human and mouse bone marrow. Our data showed that blocking of the SDF-1/CXCR4 signal axis or adding SDF-1 protein to MSCs significantly affected BMP2-induced alkaline phosphatase (ALP) activity and osteocalcin (OCN) synthesis, markers of preosteoblasts and mature osteoblasts, respectively. Moreover, disrupting the SDF-1 signaling impaired bone nodule mineralization during terminal differentiation of MSCs. Furthermore, we detected that blocking of the SDF-1 signaling inhibited the BMP2-induced early expression of Runt-related factor-2 (Runx2) and osterix (Osx), two “master” regulators of osteogenesis, and the SDF-1 effect was mediated via intracellular Smad and Erk activation. In conclusion, our results demonstrated a regulatory role of SDF-1 in BMP2-induced osteogenic differentiation of MSCs, as perturbing the SDF-1 signaling affected the differentiation of MSCs towards osteoblastic cells in response to BMP2 stimulation. These data provide novel insights into molecular mechanisms underlying MSC osteogenesis, and will contribute to the development of MSC therapies for enhancing bone formation and regeneration in broad orthopaedic situations.
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影响因子：
5.4
作者：
DApuzzo, M;Rolink, A;Moser, B
通讯作者：
Moser, B
影响因子：
82.9
作者：
Ceradini, DJ;Kulkarni, AR;Gurtner, GC
通讯作者：
Gurtner, GC
影响因子：
5.8
作者：
Hatse, S;Princen, K;Schols, D
通讯作者：
Schols, D
DOI：
10.1073/pnas.95.16.9448
发表时间：
1998-08-04
影响因子：
11.1
作者：
Ma, Q;Jones, D;Springer, TA
通讯作者：
Springer, TA
影响因子：
5.2
作者：
Ji, JF;He, BP;Tay, SSW
通讯作者：
Tay, SSW