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

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

doi:10.1038/s41420-019-0223-1

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.

Highlights

Introduction Type1 diabetes mellitus (T1DM) is a chronic metabolic disorder resulting from hypoinsulinemia due to the destruction of the pancreatic β-cells[1]
Representative dual-energy X-ray images showed that bone mass in the femurs of STZ-induced Type 1 diabetes mellitus (T1DM) mice was lower than control mice (Fig. 1b), which was further corroborated by the reduction of the bone mineral density (BMD) quantification (Fig. 1c)
T1DM is a prevalent systemic disease characterized by insulin insufficiency due to the destruction of the pancreatic beta cells[1]

Summary

Introduction

Introduction Type1 diabetes mellitus (T1DM) is a chronic metabolic disorder resulting from hypoinsulinemia due to the destruction of the pancreatic β-cells[1]. Previous studies have revealed that diabetes have direct detrimental effects on BMSCs, which in turn are responsible for diabetic osteopenia[9,10,11], suggesting that BMSCs could be a potential target in the treatment of T1DM-associated bone complications. MicroRNAs (miRNAs) are small noncoding RNAs with 19–25 nucleotides in length[12]. They mainly function as negative regulators by binding to the 3′-untranslated region (3′-UTR) of their target mRNAs, leading to mRNA degradation or translation inhibition[13,14]. Emerging evidence shows that miRNAs are widely involved in the process of osteogenic differentiation and bone formation; Official journal of the Cell Death Differentiation Association

Methods

Results

Conclusion