polo 样激酶 4（PLK4）损害人骨髓间充质干细胞（BMSC）的活力和成骨分化。
Polo Like Kinase 4 (PLK4) impairs human bone marrow mesenchymal stem cell (BMSC) viability and osteogenic differentiation.
机构信息
Department of Spine Surgery, The Second Xiangya Hospital, Central South University, 410011, China.
Department of Spine Surgery, The Second Xiangya Hospital, Central South University, 410011, China.
出版信息
Biochem Biophys Res Commun. 2021 Apr 16;549:221-228. doi: 10.1016/j.bbrc.2021.02.031. Epub 2021 Mar 9.
Human bone marrow mesenchymal stem cell (hBMSC) viability and osteogenic differentiation play a critical role in bone disorders such as osteoporosis. In the present study, we identified the aberrant PLK4 upregulation in osteoporosis and downregulation in BMSCs during osteogenic differentiation. In isolated hBMSCs, PLK4 overexpression significantly inhibited, whereas PLK4 knockdown promoted cell viability and hBMSC osteogenic differentiation. For molecular mechanism, PLK4 overexpression decreased, whereas PLK4 knockdown increased WNT1 and β-catenin protein levels and the phosphorylation of Smad1/5/8. The Wnt/β-catenin signaling antagonist Dickkopf 1 (DKK1) or the BMP-Smads antagonist LDN193189 dramatically suppressed hBMSC osteoblast differentiation, and partially attenuated the promotive effects of PLK4 knockdown on hBMSC osteogenic differentiation. Altogether, PLK4 overexpression impairs hBMSC viability and osteogenic differentiation potential, possibly through the Wnt/β-catenin signaling and BMP/Smads signaling.
人骨髓间充质干细胞（hBMSC）的活力和成骨分化在骨质疏松等骨骼疾病中起着关键作用。在本研究中，我们发现骨质疏松症中 PLK4 异常上调，成骨分化过程中 BMSCs 中 PLK4 下调。在分离的 hBMSCs 中，过表达 PLK4 显著抑制，而 PLK4 敲低则促进细胞活力和 hBMSC 成骨分化。就分子机制而言，PLK4 过表达降低，而 PLK4 敲低则增加 WNT1 和 β-catenin 蛋白水平以及 Smad1/5/8 的磷酸化。Wnt/β-catenin 信号通路拮抗剂 Dickkopf 1（DKK1）或 BMP-Smads 拮抗剂 LDN193189 显著抑制 hBMSC 成骨分化，并部分减弱 PLK4 敲低对 hBMSC 成骨分化的促进作用。总之，PLK4 过表达损害 hBMSC 的活力和成骨分化潜能，可能通过 Wnt/β-catenin 信号通路和 BMP/Smads 信号通路。
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