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Research Paper|Volume 12, Issue 10|pp 9500—9514

MiR-16-5p regulates postmenopausal osteoporosis by directly targeting VEGFA

Tao Yu1, Xiaomeng You2, Haichao Zhou1, Wenbao He1, Zihua Li1, Bing Li1, Jiang Xia1, Hui Zhu1, Youguang Zhao1, Guangrong Yu1, Yuan Xiong3, Yunfeng Yang1
  • 1Department of Orthopedic Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
  • 2Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
  • 3Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
* Equal contribution
Received: February 8, 2020Accepted: March 31, 2020Published: May 19, 2020
https://doi.org/10.18632/aging.103223

Copyright © 2020 Yu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

In this study, we used bioinformatics tools, and experiments with patient tissues and human mesenchymal stem cells (hMSCs) to identify differentially regulated genes (DEGs) and microRNAs (miRNAs) that promote postmenopausal osteoporosis. By analyzing the GSE56815 dataset from the NCBI GEO database, we identified 638 DEGs, including 371 upregulated and 267 downregulated genes, in postmenopausal women with low bone density. Enrichment and protein-protein interaction network analyses showed that TP53, RPS27A, and VEGFA were the top three hub genes with the highest degree of betweenness and closeness centrality. TargetScanHuman and DIANA software analyses and dual luciferase reporter assays confirmed that miR-16a-5p directly targets the 3’UTR of VEGFA. Postmenopausal patients with osteoporosis showed higher miR-16-5p and lower VEGFA levels than those without osteoporosis (n=10 each). VEGFA levels were higher in miR-16-5p knockdown hMSCs and were reduced in miR-16-5p-overexpressing hMSCs. mRNA expression of osteogenic markers, ALP, OCN, and RUNX2, as well as calcium deposition based on Alizarin red staining, correlated inversely with miR-16-5p levels and correlated positively with VEGFA levels. These findings suggest that miR-16-5p suppresses osteogenesis by inhibiting VEGFA expression and is a promising target for postmenopausal osteoporosis therapy.