The Regulation of Differentiation of Mesenchymal Stem-cells into Skeletal Muscle: A Look at Signalling Molecules Involved in Myogenesis

Mesenchymal Stem Cells (MSCs) are an attractive option for the development of treatment for musculoskeletal pathologies due to their wide availability, clinical safety and multiple techniques available. Understanding the control of MSC differentiation into skeletal muscle is vital for developing protocols and therapeutic applications that are safe and effective. This paper therefore aims to review the current understanding of factors that regulate the differentiation of MSCs into skeletal muscle. Medline, Embase, Pubmed and Web of Science were searched for December 2015 using the terms ‘differentia*, skeletal*, skeleton*, myocyt*, myogen* and mesenchym* stem-cell*. This returned a total of 1215 results. 48 papers were included in the review. Forty-eight studies were reviewed. Eight related to external signalling molecules, sixteen related to local environmental factors and twenty-four related to intracellular signalling pathways. Uniaxial strain, medium stiffness of the extracellular matrix and submicron grooved topography were identified as promoting myogenesis. TGF-β was identified as a main inhibitor of myogenesis. Smad and Pax signalling were identified as important intracellular pathways and the relationship of menin, Setdb1, GEFT, PAX3-FOXO1, IGF-II, TAZ and PRDM2 with MyoD and MyoG was explored. Further research into the effect of the inflammatory response on skeletal muscle differentiation is suggested. Clarification of the mechanism of action of TGF-β, the role of submicron grooves and cyclic uniaxial strain, and two important factors in the development of tissue scaffolds. Keywords: Mesenchymal stem-cells (MSCs), myogenesis, differentiation, regulation, skeletal muscle, intracellular signalling pathways, topography, TGF-b.