microRNA-21 promotes osteogenic differentiation of mesenchymal stem cells by the PI3K/β-catenin pathway.
Osteogenesis of mesenchymal stem cells (MSCs) is essential for bone repair. Recently, microRNAs have been proven to play an important role in the regulation of MSC differentiation, including osteogenesis. Here, the function of microRNA-21 (miR-21) in the osteogenic differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) was investigated. Briefly, the miR-21 mimics (m-miR-21) and the antisense miR-21 (as-miR-21) were transfected to hUMSCs, and the capacity of miR-21 for the osteogenic differentiation of hUMSCs was evaluated by the expression of osteogenic markers encoding alkaline phosphatase (ALP), runt-related gene-2 (RUNX-2) and osteocalcin (OCN), as well as by Alizarin red S staining. The results indicated that the overexpression of miR-21 elevated the expression level of the osteogenesis-related genes of hUMSCs. During this process, the PI3K-AKT signaling pathway activity had an increasing tendency responding to miR-21 up-regulation. This enhancement promoted the phosphorylation of GSK-3β, leading to the stabilization and high concentration accumulation of β-catenin in cytoplasm to activate the transcription of RUNX-2, and finally increased the osteogenesis of hUMSCs. This work demonstrated that miR-21 and its target PI3K-AKT-GSK3β pathway played an important role in the osteogenic differentiation of hUMSCs by stabilizing β-catenin.
Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, P.R. China.
Yu-Bin
YB
Meng
Department of Clinical Microbiology, School of Laboratory Medicine, Tianjin Medical University, Tianjin, 300203, P.R. China.
Xue
X
Li
Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, P.R. China.
Zhao-Yang
ZY
Li
Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, P.R. China.
Jin
J
Zhao
Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, P.R. China.
Xu-Bo
XB
Yuan
Research Center of Basic Medical Sciences & Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin Medical University, Tianjin, 300070, P.R. China.
Yu
Y
Ren
Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, P.R. China.
Zhen-Duo
ZD
Cui
Department of Clinical Microbiology, School of Laboratory Medicine, Tianjin Medical University, Tianjin, 300203, P.R. China.
Yun-De
YD
Liu
Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, P.R. China.
Xian-Jin
http://orcid.org/0000-0002-5152-9532
XJ
Yang
D002454:Cell Differentiation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D035683:MicroRNAs / Q000502:physiology*; D010012:Osteogenesis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases
PI3K/AKT/β-catenin; mesenchymal stem cells; miR-21; osteogenesis