Polo Like Kinase 4 (PLK4) impairs human bone marrow mesenchymal stem cell (BMSC) viability and osteogenic differentiation

Biochem Biophys Res Commun. 2021 Apr 16;549:221-228. doi: 10.1016/j.bbrc.2021.02.031. Epub 2021 Mar 9.

ABSTRACT

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.

PMID:33706192 | DOI:10.1016/j.bbrc.2021.02.031