Premium
MicroRNA‐200c promotes osteogenic differentiation of human bone mesenchymal stem cells through activating the AKT/β‐Catenin signaling pathway via downregulating Myd88
Author(s) -
Xia Peng,
Gu Rui,
Zhang Wei,
Shao Liwei,
Li Fang,
Wu Changyan,
Sun Yifu
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28834
Subject(s) - chemistry , microbiology and biotechnology , downregulation and upregulation , bone sialoprotein , protein kinase b , mesenchymal stem cell , alkaline phosphatase , signal transduction , pi3k/akt/mtor pathway , cellular differentiation , osteocalcin , runx2 , gene silencing , microrna , catenin , cancer research , wnt signaling pathway , biology , biochemistry , gene , enzyme
During the human bone formation, the event of osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) is vital, and recent evidence has emphasized the important role of microRNAs (miRNAs) in osteogenic differentiation of hBMSCs. This study aims to examine the potential effects of miR‐200c in osteogenic differentiation of hBMSCs and understand their underlying mechanisms. HBMSCs were obtained via human bone marrow. During osteogenic induction and differentiation, cells were transfected with different plasmids with the intention of investigating the roles of miR‐200c on osteogenic differentiation, calcium salt deposition, alkaline‐phosphatase (ALP) activity, mineralized nodule formation, osteocalcin (OCN) content, and proliferation of osteoblasts. Following transfection, dual luciferase reporter gene assay was conducted so as to explore the correlation between miR‐200c and Myd88. Moreover, the AKT/β‐Catenin signaling pathway was blocked with an AKT/β‐Catenin inhibitor, AKTi, to investigate its involvement. The hBMSCs were successfully isolated from human bone marrow. Myd88 was determined as a target gene of miR‐200c. Gain and loss‐of‐function assays confirmed that overexpression of miR‐200c, or silencing of Myd88 promoted osteogenic differentiation, increased calcium salt deposition, ALP activity, mineralized nodule formation, and enhanced the proliferation of osteoblasts following osteogenic differentiation of hBMSCs. Meanwhile, the downregulation of miR‐200c has been shown to have the opposite effect. Furthermore, these findings showed that the miR‐200c overexpression activated the AKT/β‐Catenin signaling pathway by targeting Myd88. To sum up, the miR‐200c upregulation induces osteogenic differentiation of hBMSCs by activating the AKT/β‐Catenin signaling pathway via the inhibition of Myd88, providing a target for treatment of bone repair.