Pulsed Electromagnetic Fields Modulate miRNAs During Osteogenic Differentiation of Bone Mesenchymal Stem Cells: a Possib
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Pulsed Electromagnetic Fields Modulate miRNAs During Osteogenic Differentiation of Bone Mesenchymal Stem Cells: a Possible Role in the Osteogenic-angiogenic Coupling Monica De Mattei 1 & Silvia Grassilli 2,3 & Agnese Pellati 2 & Federica Brugnoli 2 & Elena De Marchi 1 & Deyanira Contartese 1,4 & Valeria Bertagnolo 2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Despite the high intrinsic ability of bone tissue to regenerate, bone healing fails in some pathological conditions and especially in the presence of large defects. Due to the strong relationship between bone development and vascularization during in vivo bone formation and repair, strategies promoting the osteogenic-angiogenic coupling are crucial for regenerative medicine. Increasing evidence shows that miRNAs play important roles in controlling osteogenesis and bone vascularization and are important tool in medical research although their clinical use still needs to optimize miRNA stability and delivery. Pulsed electromagnetic fields (PEMFs) have been successfully used to enhance bone repair and their clinical activity has been associated to their ability to promote the osteogenic differentiation of human mesenchymal stem cells (hMSCs). In this study we investigated the potential ability of PEMF exposure to modulate selected miRNAs involved in the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). We show that, during in vitro hBMSC differentiation, PEMFs up-modulate the expression of miR-26a and miR-29b, which favor osteogenic differentiation, and decrease miR-125b which acts as an inhibitor miRNA. As PEMFs promote the expression and release of miRNAs also involved in angiogenesis, we conclude that PEMFs may represent a noninvasive and safe strategy to modulate miRNAs with relevant roles in bone repair and with the potential to regulate the osteogenic-angiogenic coupling. Keywords Bone repair . Osteogenic differentiation . Human bone mesenchymal stem cells (hBMSCs) . Pulsed electromagnetic field (PEMF) . miRNAs . Osteogenic-angiogenic coupling
Introduction Bone repair is a complex multistep process which involves differentiation of mesenchymal stem cells (MSCs) into osteoblasts and requires coordinated coupling between osteogenesis and angiogenesis [1, 2]. Increasing body of evidence
* Monica De Mattei [email protected] * Valeria Bertagnolo [email protected] 1
Department of Medical Sciences, University of Ferrara, Ferrara, Italy
2
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy
3
LTTA Centre, University of Ferrara, Ferrara, Italy
4
Laboratory Preclinical and Surgical Studies, IRCCS-Istituto Ortopedico Rizzoli, Bologna, Italy
supports the crucial role of microRNAs (miRNAs) in bone development and homeostasis [3, 4] and in promoting MSC osteogenic differentiation [5, 6]. Complex interactions among miRNAs coordinate osteogenesis and angiogenesis during development, remodeling and regeneration of the skeletal system [7]. The strategies impr
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