High-glucose-induced miR-214-3p inhibits BMSCs osteogenic differentiation in type 1 diabetes mellitus

Rongze Wang; Yuanxu Zhang; Fujun Jin; Gongchen Li; Yao Sun; Xiaogang Wang

doi:10.1038/s41420-019-0223-1

High-glucose-induced miR-214-3p inhibits BMSCs osteogenic differentiation in type 1 diabetes mellitus

Cell Death Discov. 2019 Nov 12:5:143. doi: 10.1038/s41420-019-0223-1. eCollection 2019.

Authors

Rongze Wang^#¹, Yuanxu Zhang^#², Fujun Jin^{2

3}, Gongchen Li⁴, Yao Sun⁴, Xiaogang Wang^{1

5}

Affiliations

¹ 1Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
² 2Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
³ 3Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China.
⁴ 4Department of Oral Implantology, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
⁵ 5Clinical Research Platform for Interdiscipline of Stomatology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.

^# Contributed equally.

Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune insulin-dependent disease associated with destructive bone homeostasis. Accumulating evidence has proven that miRNAs are widely involved in the regulation of bone homeostasis. However, whether miRNAs also regulate osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in T1DM mice is under exploration. In this study, miRNA microarray was utilized to screen the differentially expressed miRNAs, which uncovered that miR-214-3p potentially inhibited BMSCs osteogenic differentiation in T1DM mice. We found that high glucose suppressed BMSCs osteogenic differentiation with significant elevation of the miR-214-3p expression. Further study found that the osteogenic differentiation of BMSCs was inhibited by AgomiR-214-3p while enhanced by AntagomiR-214-3p in BMSCs supplemented with high glucose. Moreover, we found that miR-214-3p knockout T1DM mice were resistant to high-glucose-induced bone loss. These results provide a novel insight into an inhibitory role of high-glucose-induced miR-214-3p in BMSCs osteogenic differentiation both in vitro and in vivo. Molecular studies revealed that miR-214-3p inhibits BMSCs osteogenic differentiation by targeting the 3'-UTR of β-catenin, which was further corroborated in human bone specimens and BMSCs of T1DM patients. Taken together, our study discovered that miR-214-3p is a pivotal regulator of BMSCs osteogenic differentiation in T1DM mice. Our findings also suggest that miR-214-3p could be a potential target in the treatment of bone disorders in patients with T1DM.

Keywords: Differentiation; Diseases; RNA.