MicroRNA-23 suppresses osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting the MEF2C-mediated MAPK signaling pathway.
Bone Marrow Cells
/ metabolism
Cell Differentiation
/ genetics
Gene Expression Regulation, Neoplastic
/ genetics
Humans
MAP Kinase Signaling System
/ genetics
MEF2 Transcription Factors
/ genetics
Mesenchymal Stem Cells
/ metabolism
MicroRNAs
/ genetics
Osteoblasts
/ metabolism
Osteogenesis
/ genetics
MAPK
Osteogenesis
RNA, miR-23
mesenchymal stromal cells
Journal
The journal of gene medicine
ISSN: 1521-2254
Titre abrégé: J Gene Med
Pays: England
ID NLM: 9815764
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
27
02
2020
revised:
21
04
2020
accepted:
21
04
2020
pubmed:
16
5
2020
medline:
19
8
2021
entrez:
16
5
2020
Statut:
ppublish
Résumé
The present study aimed to determine the role and mechanism of miR-23 with respect to regulating the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The expression of miR-23 and MEF2C was measured in osteoporosis (OP) patients and healthy controls by a quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The correlation between miR-23 and MEF2C was determined by the Pearson correlation coefficient. Moreover, bioinformatic analysis was performed using public databases. Target gene function and potential pathways were further examined. Then, we used a miR-23 mimic or inhibitor to further explore the potential mechanism of miR-23. miR-23 is found to be up-regulated and MEF2C is down-regulated in OP patients compared to healthy controls. miR-23 had a negative correlation with MEF2C (r = -0.937, p = 0.001). Bioinformatic analysis revealed that a total of 664 overlapping target genes were found in the TargetScan (http://www.targetscan.org), miRDB (http://mirdb.org) and miRanda (http://www.microrna.org/microrna/home.do) databases. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that miR-23 may regulate the mitogan-activated protein kinase (MAPK) signaling pathway. miR-23 is down-regulated and MEF2C is significantly up-regulated in the osteogenic differentiation of hBMSCs. MEF2C was significantly up-regulated in the osteogenic differentiation of hBMSCs. Overexpression of miR-23 significantly down-regulated alkaline phosphatase (ALP) activity and calcium deposition, whereas the miR-23 inhibitor had the opposite effects. Moreover, overexpression of miR-23 significantly decreased osteoblast-related markers (Runx2, Osx, ALP and OCN). Further experiments confirmed that MEF2C is a direct target of miR-23. Moreover, the miR-23 mimic enhanced the expression of p-p38 but had no effect on p-JNK. miR-23 decreases the osteogenic differentiation of hBMSCs through the MEF2C/MAPK signaling pathway.
Sections du résumé
BACKGROUND
The present study aimed to determine the role and mechanism of miR-23 with respect to regulating the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs).
MATERIALS
The expression of miR-23 and MEF2C was measured in osteoporosis (OP) patients and healthy controls by a quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The correlation between miR-23 and MEF2C was determined by the Pearson correlation coefficient. Moreover, bioinformatic analysis was performed using public databases. Target gene function and potential pathways were further examined. Then, we used a miR-23 mimic or inhibitor to further explore the potential mechanism of miR-23.
RESULTS
miR-23 is found to be up-regulated and MEF2C is down-regulated in OP patients compared to healthy controls. miR-23 had a negative correlation with MEF2C (r = -0.937, p = 0.001). Bioinformatic analysis revealed that a total of 664 overlapping target genes were found in the TargetScan (http://www.targetscan.org), miRDB (http://mirdb.org) and miRanda (http://www.microrna.org/microrna/home.do) databases. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that miR-23 may regulate the mitogan-activated protein kinase (MAPK) signaling pathway. miR-23 is down-regulated and MEF2C is significantly up-regulated in the osteogenic differentiation of hBMSCs. MEF2C was significantly up-regulated in the osteogenic differentiation of hBMSCs. Overexpression of miR-23 significantly down-regulated alkaline phosphatase (ALP) activity and calcium deposition, whereas the miR-23 inhibitor had the opposite effects. Moreover, overexpression of miR-23 significantly decreased osteoblast-related markers (Runx2, Osx, ALP and OCN). Further experiments confirmed that MEF2C is a direct target of miR-23. Moreover, the miR-23 mimic enhanced the expression of p-p38 but had no effect on p-JNK.
CONCLUSIONS
miR-23 decreases the osteogenic differentiation of hBMSCs through the MEF2C/MAPK signaling pathway.
Substances chimiques
MEF2 Transcription Factors
0
MEF2C protein, human
0
MIRN23a microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3216Informations de copyright
© 2020 John Wiley & Sons, Ltd.
Références
Li Y, Feng C, Gao M, et al. MicroRNA-92b-5p modulates melatonin-mediated osteogenic differentiation of bone marrow mesenchymal stem cells by targeting ICAM-1. J Cell Mol Med. 2019;23:6140-6153.
Ma S, Wang DD, Ma CY, et al. microRNA-96 promotes osteoblast differentiation and bone formation in ankylosing spondylitis mice through activating the Wnt signaling pathway by binding to SOST. 2019;120:15429-15442.
Abdallah BM, Ali EM. 5′-hydroxy Auraptene stimulates osteoblast differentiation of bone marrow-derived mesenchymal stem cells via a BMP-dependent mechanism. J Biomed Sci. 2019;26:51-51.
Tang Y, Shen J, Zhang F, Yang FY, Liu M. Human serum albumin attenuates global cerebral ischemia/reperfusion-induced brain injury in a Wnt/beta-catenin/ROS signaling-dependent manner in rats. Biomed Pharmacother. 2019;115:108871-108871.
He H, He Q, Xu F, Zhou Y, Ye Z, Tan WS. Dynamic formation of cellular aggregates of chondrocytes and mesenchymal stem cells in spinner flask. Cell Prolif. 2019;52:e12587-e12587.
Galhom RA, Hussein Abd El Raouf HH, Mohammed Ali MH. Role of bone marrow derived mesenchymal stromal cells and Schwann-like cells transplantation on spinal cord injury in adult male albino rats. Biomed Pharmacother. 2018;108:1365-1375.
Han Y, Li X, Zhang Y. Mesenchymal stem cells for regenerative medicine. Cell. 2019;8:pii: E886-E886.
Hao W, Liu H, Zhou L, et al. MiR-145 regulates osteogenic differentiation of human adipose-derived mesenchymal stem cells through targeting FoxO1. Exp Biol Med (Maywood). 2018;243:386-393.
Zhang L, Tang Y, Zhu X, et al. Overexpression of MiR-335-5p promotes bone formation and regeneration in mice. J Bone Miner Res. 2017;32:2466-2475.
Li JP, Zhuang HT, Xin MY, Zhou YL. MiR-214 inhibits human mesenchymal stem cells differentiating into osteoblasts through targeting beta-catenin. Eur Rev Med Pharmacol Sci. 2017;21:4777-4783.
Hassan MQ, Gordon JA, Beloti MM, et al. A network connecting Runx2, SATB2, and the miR-23a~27a~24-2 cluster regulates the osteoblast differentiation program. Proc Natl Acad Sci U S A. 2010;107:19879-19884.
Wang Q, Li Y, Zhang Y, et al. LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p. Biomed Pharmacother. 2017;89:1178-1186.
Tao K, Xiao D, Weng J, Xiong A, Kang B, Zeng H. Berberine promotes bone marrow-derived mesenchymal stem cells osteogenic differentiation via canonical Wnt/beta-catenin signaling pathway. Toxicol Lett. 2016;240:68-80.
Liu Y, Tan J, Ou S, Chen J, Chen L. Adipose-derived exosomes deliver miR-23a/b to regulate tumor growth in hepatocellular cancer by targeting the VHL/HIF axis. J Physiol Biochem. 2019;75:391-401.
Yu RB, Li K, Wang G, Gao GM, du JX. MiR-23 enhances cardiac fibroblast proliferation and suppresses fibroblast apoptosis via targeting TGF-beta1 in atrial fibrillation. Eur Rev Med Pharmacol Sci. 2019;23:4419-4424.
Liu L, Cheng Z, Yang J. miR-23 regulates cell proliferation and apoptosis of vascular smooth muscle cells in coronary heart disease. Pathol Res Pract. 2018;214:1873-1878.
Godfrey TC, Wildman BJ, Beloti MM, et al. The microRNA-23a cluster regulates the developmental HoxA cluster function during osteoblast differentiation. J Biol Chem. 2018;293:17646-17660.
Yavropoulou MP, Anastasilakis AD, Makras P, Tsalikakis DG, Grammatiki M, Yovos JG. Expression of microRNAs that regulate bone turnover in the serum of postmenopausal women with low bone mass and vertebral fractures. Eur J Endocrinol. 2017;176:169-176.
Nakatani T, Partridge NC. MEF2C interacts with c-FOS in PTH-stimulated Mmp13 gene expression in osteoblastic cells. Endocrinology. 2017;158:3778-3791.
Wein MN, Spatz J, Nishimori S, et al. HDAC5 controls MEF2C-driven sclerostin expression in osteocytes. J Bone Miner Res. 2015;30:400-411.
Saidak Z, Le Henaff C, Azzi S, et al. Low-dose PTH increases osteoblast activity via decreased Mef2c/Sost in senescent osteopenic mice. J Endocrinol. 2014;223:25-33.
Wang Z, Wang D, Yang D, Zhen W, Zhang J, Peng S. The effect of icariin on bone metabolism and its potential clinical application. Osteoporos Int. 2018;29:535-544.
Jiao F, Tang W, Huang H, et al. Icariin promotes the migration of BMSCs in vitro and in vivo via the MAPK signaling pathway. Stem Cells Int. 2018;2018:2562105-2562109.
Xing LZ, Ni HJ, Wang YL. Quercitrin attenuates osteoporosis in ovariectomized rats by regulating mitogen-activated protein kinase (MAPK) signaling pathways. Biomed Pharmacother. 2017;89:1136-1141.
Auh QS, Park KR, Yun HM, et al. Sulfuretin promotes osteoblastic differentiation in primary cultured osteoblasts and in vivo bone healing. Oncotarget. 2016;7:78320-78330.
Wang Z, Liu Q, Liu C, et al. Mg(2+) in β-TCP/mg-Zn composite enhances the differentiation of human bone marrow stromal cells into osteoblasts through MAPK-regulated Runx2/Osx. J Cell Physiol. 2020;235:5182-5191.
Li C, Yang X, He Y, et al. Bone morphogenetic protein-9 induces osteogenic differentiation of rat dental follicle stem cells in P38 and ERK1/2 MAPK dependent manner. Int J Med Sci. 2012;9:862-871.
Zhang Y, Liu X, Zeng L, et al. Polymer fiber scaffolds for bone and cartilage tissue engineering. Adv Funct Mater. 2019;29:1903279-1903279.
Ding J, Zhang J, Li J, et al. Electrospun polymer biomaterials. Prog Polym Sci. 2019;90:1-34.
Feng X, Li J, Zhang X, Liu T, Ding J, Chen X. Electrospun polymer micro/nanofibers as pharmaceutical repositories for healthcare. J Control Release. 2019;302:19-41.