Tenogenic Contribution to Skeletal Muscle Regeneration: The Secretome of Scleraxis Overexpressing Mesenchymal Stem Cells Enhances Myogenic Differentiation In Vitro

Strenzke, Maximilian and Alberton, Paolo and Aszodi, Attila and Docheva, Denitsa and Haas, Elisabeth and Kammerlander, Christian and Boecker, Wolfgang and Saller, Maximilian Michael (2020) Tenogenic Contribution to Skeletal Muscle Regeneration: The Secretome of Scleraxis Overexpressing Mesenchymal Stem Cells Enhances Myogenic Differentiation In Vitro. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (6): 1965. ISSN , 1422-0067

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Abstract

Integrity of the musculoskeletal system is essential for the transfer of muscular contraction force to the associated bones. Tendons and skeletal muscles intertwine, but on a cellular level, the myotendinous junctions (MTJs) display a sharp transition zone with a highly specific molecular adaption. The function of MTJs could go beyond a mere structural role and might include homeostasis of this musculoskeletal tissue compound, thus also being involved in skeletal muscle regeneration. Repair processes recapitulate several developmental mechanisms, and as myotendinous interaction does occur already during development, MTJs could likewise contribute to muscle regeneration. Recent studies identified tendon-related, scleraxis-expressing cells that reside in close proximity to the MTJs and the muscle belly. As the muscle-specific function of these scleraxis positive cells is unknown, we compared the influence of two immortalized mesenchymal stem cell (MSC) lines-differing only by the overexpression of scleraxis-on myoblasts morphology, metabolism, migration, fusion, and alignment. Our results revealed a significant increase in myoblast fusion and metabolic activity when exposed to the secretome derived from scleraxis-overexpressing MSCs. However, we found no significant changes in myoblast migration and myofiber alignment. Further analysis of differentially expressed genes between native MSCs and scleraxis-overexpressing MSCs by RNA sequencing unraveled potential candidate genes, i.e., extracellular matrix (ECM) proteins, transmembrane receptors, or proteases that might enhance myoblast fusion. Our results suggest that musculotendinous interaction is essential for the development and healing of skeletal muscles.

Item Type: Article
Uncontrolled Keywords: PROGENITOR CELLS; SATELLITE CELLS; MIGRATION; INJURY; MORPHOGENESIS; MACROPHAGES; EXPRESSION; MITOGEN; tendon-muscle crosstalk; myotendinous junction; regenerative medicine; skeletal muscle; scleraxis; mesenchymal stem cells; satellite cell; RNA-Seq
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Unfallchirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 29 Mar 2021 10:17
Last Modified: 29 Mar 2021 10:17
URI: https://pred.uni-regensburg.de/id/eprint/44985

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