Regulative Effect of Mir-205 on Osteogenic Differentiation of Bone Mesenchymal Stem Cells (BMSCs): Possible Role of SATB2/Runx2 and ERK/MAPK Pathway.

Nan Hu,Qing Miao,Yi Jiang,Chunzhen Feng,Hongchen Liu

doi:10.3390/ijms160510491

Abstract

Bone mesenchymal stem cells (BMSCs) have multiple potentials to differentiate into osteoblasts and adipocytes, and methods to enhance their osteogenic differentiation are gaining increasing attention. MicroRNAs are critical regulation factors during the process of the osteogenic induction in BMSCs, and mir-205 has been substantiated to be involved in the osteogenic process, but the underlying mechanisms remain unclear. The purpose of this article is to investigate the role of mir-205 in the osteogenic differentiation of BMSCs. We found that mir-205 expression was down-regulated in a time-dependent manner during BMSC osteo-induction. Inhibition of mir-205 enhanced osteogenic abilities by up-regulating bone sialoprotein (BSP) and osteopontin (OPN) protein levels and increasing alkaline phosphatase (ALP) activity and osteocalcin secretion. Furthermore, we found that mir-205 could regulate protein expression of special AT-rich sequence-binding protein 2 (SATB2) and runt-related transcription factor 2 (Runx2), and over-expression of SATB2 activated Runx2 and reversed the negative effects of mir-205 on osteoblastic differentiation. Furthermore, we examined the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) pathways during osteogenic induction and our data indicates that mir-205 might exert negative functions on the osteogenic differentiation in BMSCs at least partly via altering phosphorylation of ERK and p38 MAPK. These results shed new light on the molecular mechanisms of microRNAs in governing differentiation of BMSCs.

Highlights

Bone mesenchymal stem cells (BMSCs), isolated from the bone marrow by Friedenstein et al [1], have multiple differentiation potentials
The present study provides the detailed observations regarding the effects of mir-205 on osteogenic differentiation and possible mechanisms in BMSCs
Mir-205 negatively regulates osteoblastic differentiation via inhibiting the expression of Runx2 and SATB2, and the possible mechanisms may be mediated by the extracellular signal-regulated kinase (ERK) and p38 mitogen activated protein kinase (MAPK) pathways

Summary

Introduction

Bone mesenchymal stem cells (BMSCs), isolated from the bone marrow by Friedenstein et al [1], have multiple differentiation potentials. Numerous studies have shown that BMSCs can differentiate into osteoblasts, chondrocytes and adipocytes [2]. BMSCs even substitute for neural progenitor cells (NPCs) in restorative therapy for stroke [3]. BMSCs can differentiate into osteoblasts, which makes them a suitable cell type in bone repair and tissue engineering [4,5,6,7]. The osteogenic differentiation of BMSCs can be regulated by multiple signaling molecules and transcriptional regulators, and how to enhance the osteogenic differentiation of BMSCs has gained increasing attention in recent years. MicroRNAs (miRNA) are small RNA molecules that bind to the non-coding region of mRNA and regulate mRNA activity by inducing mRNA degradation or suppressing mRNA activity [8,9]

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