MiR-26a Rescues Bone Regeneration Deficiency of Mesenchymal Stem Cells Derived From Osteoporotic Mice
MiR-26a Rescues Bone Regeneration Deficiency of Mesenchymal Stem Cells Derived From Osteoporotic Mice
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DOI：
10.1038/mt.2015.101
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发表时间：
2015-08-01
影响因子：
12.4
通讯作者：
Jin, Yan
中科院分区：
文献类型：
--
作者：
Li, Yan;Fan, Longkun;Jin, Yan
骨质疏松症是由于骨吸收相对于骨形成的增加而引起的，其特点是骨量和骨强度下降，导致骨折发生率增加，骨质愈合能力受损往往导致老年人进一步残疾和早期死亡。目前临床上用于治疗骨质疏松症的药物主要是抗骨吸收药物，通过降低骨吸收率来发挥其临床作用。然而，仅针对抗骨吸收的策略在恢复骨重塑平衡和促进骨质疏松性骨折愈合方面的治疗效果有限。在这里，我们报道miR-26a在骨质疏松症期间调节骨形成中起关键作用。我们发现，miR-26a处理能有效提高窝源性去卵巢骨质疏松小鼠间充质干细胞的体外和体内成骨分化能力。MiR-26a通过结合3'-非翻译区，直接靶向BMP/Smad信号通路的负调控因子Tob1，从而抑制Tob1蛋白的表达，从而发挥作用。我们的研究结果表明，miR-26a可能是一种有希望的治疗候选者，在骨质疏松症治疗中促进骨形成，在骨质疏松性骨折愈合中促进骨再生。
Osteoporosis, caused by a relative increase of bone resorption over bone formation, is characterized by decreased bone mass and bone strength, resulting in an increased incidence of bone fractures, which often leads to further disability and early mortality in the elderly due to impaired bone healing ability. The majority of therapeutics currently used in clinics for the treatment of osteoporosis are antiresorptive agents that exert their clinical effect by decreasing the rate of bone resorption. However, strategies solely aimed at antiresorption have limited therapeutic efficacy in restoring bone remodeling balance and enhancing osteoporotic fracture healing. Here, we report that miR-26a plays a critical role in modulating bone formation during osteoporosis. We found that miR-26a treatment could effectively improve the osteogenic differentiation capability of mesenchymal stem cells isolated from littermate-derived ovariectomized osteoporotic mice both in vitro and in vivo. MiR-26a exerts its effect by directly targeting Tob1, the negative regulator of BMP/Smad signaling pathway by binding to the 3'-untranslated region and thus repressing Tob1 protein expression. Our findings indicate that miR-26a may be a promising therapeutic candidate to enhance bone formation in treatment of osteoporosis and to promote bone regeneration in osteoporotic fracture healing.