Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation

Pulsed electromagnetic fields (PEMFs) have been documented to promote bone fracture healing in nonunions and increase lumbar spinal fusion rates. However, the molecular mechanisms by which PEMF stimulates differentiation of human bone marrow stromal cells (hBMSCs) into osteoblasts are not well under...

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Main Authors: Nagarajan Selvamurugan, Zhiming He, Daniel Rifkin, Branka Dabovic, Nicola C. Partridge
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2017/2450327
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author Nagarajan Selvamurugan
Zhiming He
Daniel Rifkin
Branka Dabovic
Nicola C. Partridge
author_facet Nagarajan Selvamurugan
Zhiming He
Daniel Rifkin
Branka Dabovic
Nicola C. Partridge
author_sort Nagarajan Selvamurugan
collection DOAJ
description Pulsed electromagnetic fields (PEMFs) have been documented to promote bone fracture healing in nonunions and increase lumbar spinal fusion rates. However, the molecular mechanisms by which PEMF stimulates differentiation of human bone marrow stromal cells (hBMSCs) into osteoblasts are not well understood. In this study the PEMF effects on hBMSCs were studied by microarray analysis. PEMF stimulation of hBMSCs’ cell numbers mainly affected genes of cell cycle regulation, cell structure, and growth receptors or kinase pathways. In the differentiation and mineralization stages, PEMF regulated preosteoblast gene expression and notably, the transforming growth factor-beta (TGF-β) signaling pathway and microRNA 21 (miR21) were most highly regulated. PEMF stimulated activation of Smad2 and miR21-5p expression in differentiated osteoblasts, and TGF-β signaling was essential for PEMF stimulation of alkaline phosphatase mRNA expression. Smad7, an antagonist of the TGF-β signaling pathway, was found to be miR21-5p’s putative target gene and PEMF caused a decrease in Smad7 expression. Expression of Runx2 was increased by PEMF treatment and the miR21-5p inhibitor prevented the PEMF stimulation of Runx2 expression in differentiating cells. Thus, PEMF could mediate its effects on bone metabolism by activation of the TGF-β signaling pathway and stimulation of expression of miR21-5p in hBMSCs.
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spelling doaj-art-3bd3b2d9afb842e2a95373fcc327052b2025-02-03T01:02:11ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/24503272450327Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast DifferentiationNagarajan Selvamurugan0Zhiming He1Daniel Rifkin2Branka Dabovic3Nicola C. Partridge4Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Tamil Nadu, IndiaDepartment of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, USADepartment of Cell Biology, New York University School of Medicine, New York, NY, USADepartment of Cell Biology, New York University School of Medicine, New York, NY, USADepartment of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, USAPulsed electromagnetic fields (PEMFs) have been documented to promote bone fracture healing in nonunions and increase lumbar spinal fusion rates. However, the molecular mechanisms by which PEMF stimulates differentiation of human bone marrow stromal cells (hBMSCs) into osteoblasts are not well understood. In this study the PEMF effects on hBMSCs were studied by microarray analysis. PEMF stimulation of hBMSCs’ cell numbers mainly affected genes of cell cycle regulation, cell structure, and growth receptors or kinase pathways. In the differentiation and mineralization stages, PEMF regulated preosteoblast gene expression and notably, the transforming growth factor-beta (TGF-β) signaling pathway and microRNA 21 (miR21) were most highly regulated. PEMF stimulated activation of Smad2 and miR21-5p expression in differentiated osteoblasts, and TGF-β signaling was essential for PEMF stimulation of alkaline phosphatase mRNA expression. Smad7, an antagonist of the TGF-β signaling pathway, was found to be miR21-5p’s putative target gene and PEMF caused a decrease in Smad7 expression. Expression of Runx2 was increased by PEMF treatment and the miR21-5p inhibitor prevented the PEMF stimulation of Runx2 expression in differentiating cells. Thus, PEMF could mediate its effects on bone metabolism by activation of the TGF-β signaling pathway and stimulation of expression of miR21-5p in hBMSCs.http://dx.doi.org/10.1155/2017/2450327
spellingShingle Nagarajan Selvamurugan
Zhiming He
Daniel Rifkin
Branka Dabovic
Nicola C. Partridge
Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation
Stem Cells International
title Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation
title_full Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation
title_fullStr Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation
title_full_unstemmed Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation
title_short Pulsed Electromagnetic Field Regulates MicroRNA 21 Expression to Activate TGF-β Signaling in Human Bone Marrow Stromal Cells to Enhance Osteoblast Differentiation
title_sort pulsed electromagnetic field regulates microrna 21 expression to activate tgf β signaling in human bone marrow stromal cells to enhance osteoblast differentiation
url http://dx.doi.org/10.1155/2017/2450327
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