MiRNA-187-5p Regulates Osteoblastic Differentiation of Bone Marrow Mesenchymal Stem Cells in Mice by Targeting ICAM1.

Yi Sun,Yutuo Fu,Guanghua Chen,Chengchao Song,Jinglong Yan,Xin Wang,Chao Feng,Xinnan Ma,Junyan Liu

doi:10.1155/2020/6139469

Abstract

Osteoporosis (OP) is a common bone metabolic disease, the process of which is fundamentally irreversible. Therefore, the investigation into osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) will provide more clues for OP treatment. In the present study, we found that microRNA-187-5p (miR-187-5p) played a key role on osteoblastic differentiation, which was significantly upregulated during osteogenic differentiation of BMSCs in mice. Moreover, overexpression of miR-187-5p suppressed osteoblastic differentiation of BMSCs through increasing alkaline phosphatase (ALP), matrix mineralization, and levels of Osterix (OSX), and osteopontin (OPN) as well as runt-related transcription factor 2 (Runx2) in vitro. The results in vivo indicated that the upregulation of miR-187-5p enhanced the efficacy of new bone formation in the heterotopic bone formation assay. Luciferase reporter assay and western blot analysis revealed that miR-187-5p was involved in osteogenesis by targeting intracellular adhesion molecule 1 (ICAM-1). Furthermore, ICAM-1 silence inhibited osteoblastic differentiation of BMSCs. Taken together, our results suggested for the first time that miR-187-5p may promote osteogenesis by targeting ICAM-1, and provided a possible therapeutic target for bone metabolic diseases.

Highlights

Millions of older adults throughout the world are suffering from osteoporosis, especially in postmenopausal women
We found that intracellular adhesion molecule 1 (ICAM-1) was a target of miR-187-5p and the regulatory mechanism of miR-187-5p/ICAM-1 in Bone marrow-derived mesenchymal stem cells (BMSCs) into osteogenic differentiation was evaluated, which could reveal a new mechanism and provide a novel therapeutic target for age-related bone loss
After 24 h of transfection of miR-187-5p mimics, mimics-negative control (NC), miR-187-5p inhibitor, and inhibitor-NC, BMSCs were cultured to osteogenicinduced medium (OM-CTL) and normal growth medium culture (NM-CTL), and the mineral nodules were determined by alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining

Summary

Introduction

Millions of older adults throughout the world are suffering from osteoporosis, especially in postmenopausal women. Osteoporosis (OP) is the most common metabolic bone disease because of the unbalance between new bone formation by osteoblasts and old bone resorption by osteoclasts [1]. Osteoporosis is caused by the dysfunction of bone metabolism which is characterized with low bone mass, leading to reduced bone mineral density and subsequent elevated risk of fractures [2]. Bone marrow-derived mesenchymal stem cells (BMSCs) are stromal cells with the potential of continuous self-renewal and multidirectional differentiation to osteoblasts, chondrocytes, and adipocytes [3, 4]. It has been reported that reduced bone formation and increased marrow fat accumulation are major characterizations of age-related osteoporosis [5]. Enhancing BMSC differentiation into osteoblasts may increase bone formation and improve the pathophysiological status of OP

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