Osteogenic response of mesenchymal stem cells to continuous mechanical strain is dependent on ERK1/2-Runx2 signaling.
Osteogenic response of mesenchymal stem cells to continuous mechanical strain is dependent on ERK1/2-Runx2 signaling.
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DOI：
10.3892/ijmm.2012.934
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发表时间：
2012-06
影响因子：
5.4
通讯作者：
Peng Zhang;Yuqiong Wu;Zong-Lai Jiang;Lingyong Jiang;B. Fang
中科院分区：
文献类型：
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作者：
Peng Zhang;Yuqiong Wu;Zong-Lai Jiang;Lingyong Jiang;B. Fang
在正畸牙齿运动过程中，机械刺激负责骨重塑。机械刺激在调节骨间充质干细胞（BMSCs）命运中的作用是骨再生和组织工程应用的兴趣。然而，在骨髓间充质干细胞中，参与菌株诱导的生化事件的信号通路尚未很好地确定，并且可能存在争议。本研究探讨了菌株诱导骨髓间充质干细胞的增殖和分化，以及其机械转导的机制。将骨髓间充质干细胞暴露在10%的连续机械应变（CMS）下，频率为1 Hz。结果表明，CMS通过激活Runx2抑制骨髓间充质干细胞的增殖，促进成骨分化，进而增加碱性磷酸酶（ALP）活性和成骨相关基因（ALP、I型胶原和骨钙素）mRNA表达。细胞外调节蛋白激酶（ERK）1/2的磷酸化水平在菌株开始时显著升高。然而，ERK1/2的选择性抑制剂U0126的存在阻断了Runx2的诱导和随后的成骨事件。这些发现表明，CMS通过激活ERK1/2信号通路调控Runx2激活，促进成骨细胞分化。这些结果将有助于更好地理解应变诱导骨重塑，并为正畸治疗中正确选择施加力提供依据。
Mechanical stimuli are responsible for bone remodeling during orthodontic tooth movement. The role of mechanical stimulation in the regulation of the fate of bone mesenchymal stem cells (BMSCs) is of interest in bone regeneration and tissue engineering applications. However, the signaling pathway involved in strain-induced biochemical events in BMSCs is not well established and can be controversial. This study investigated strain-induced proliferation and differentiation of BMSCs, as well as the mechanism of mechanotransduction. BMSCs were exposed to continuous mechanical strain (CMS) of 10% at 1 Hz. The results showed that CMS reduced the proliferation of BMSCs and stimulated osteogenic differentiation by activating Runx2, followed by increased alkaline phosphatase (ALP) activity and mRNA expression of osteogenesis-related genes (ALP, collagen type I and osteocalcin). Furthermore, the phosphorylation level of extracellular regulated protein kinase (ERK)1/2 increased significantly at the onset of strain. However, the presence of U0126, a selective inhibitor of ERK1/2, blocked the induction of Runx2 and subsequent osteogenic events. These findings demonstrate that CMS regulated Runx2 activation and favored osteoblast differentiation through activation of the ERK1/2 signaling pathway. These results will contribute to a better understanding of strain-induced bone remodeling and will form the basis for the correct choice of applied force in orthodontic treatment.