Frese, Sebastian Ruebner, Matthias Suhr, Frank M. Konou, Thierry A. Tappe, Kim Toigo, Marco H. Jung, Hans Henke, Christine Steigleder, Ruth L. Strissel, Pamela Huebner, Hanna W. Beckmann, Matthias van der Keylen, Piet Schoser, Benedikt Schiffer, Thorsten Frese, Laura Bloch, Wilhelm Strick, Reiner Long-Term Endurance Exercise in Humans Stimulates Cell Fusion of Myoblasts along with Fusogenic Endogenous Retroviral Genes <i>In Vivo</i> <div><p>Myogenesis is defined as growth, differentiation and repair of muscles where cell fusion of myoblasts to multinucleated myofibers is one major characteristic. Other cell fusion events in humans are found with bone resorbing osteoclasts and placental syncytiotrophoblasts. No unifying gene regulation for natural cell fusions has been found. We analyzed skeletal muscle biopsies of competitive cyclists for muscle-specific attributes and expression of human endogenous retrovirus (ERV) envelope genes due to their involvement in cell fusion of osteoclasts and syncytiotrophoblasts. Comparing muscle biopsies from post- with the pre-competitive seasons a significant 2.25-fold increase of myonuclei/mm fiber, a 2.38-fold decrease of fiber area/nucleus and a 3.1-fold decrease of satellite cells (SCs) occurred. We propose that during the pre-competitive season SC proliferation occurred following with increased cell fusion during the competitive season. Expression of twenty-two envelope genes of muscle biopsies demonstrated a significant increase of putative muscle-cell fusogenic genes <i>Syncytin-1</i> and <i>Syncytin-3</i>, but also for the non-fusogenic <i>erv3</i>. Immunohistochemistry analyses showed that <i>Syncytin-1</i> mainly localized to the sarcolemma of myofibers positive for myosin heavy-chain isotypes. Cellular receptors <i>SLC1A4</i> and <i>SLC1A5</i> of Syncytin-1 showed significant decrease of expression in post-competitive muscles compared with the pre-competitive season, but only SLC1A4 protein expression localized throughout the myofiber. Erv3 protein was strongly expressed throughout the myofiber, whereas envK1-7 localized to SC nuclei and myonuclei. Syncytin-1 transcription factors, PPARγ and RXRα, showed no protein expression in the myofiber, whereas the pCREB-Ser133 activator of Syncytin-1 was enriched to SC nuclei and myonuclei. <i>Syncytin</i>-1, <i>Syncytin</i>-3, <i>SLC1A4</i> and <i>PAX7</i> gene regulations along with <i>MyoD1</i> and <i>myogenin</i> were verified during proliferating or actively-fusing human primary myoblast cell cultures, resembling muscle biopsies of cyclists. Myoblast treatment with anti-Synycytin-1 abrogated cell fusion in vitro. Our findings support functional roles for ERV envelope proteins, especially Syncytin-1, contributing to cell fusion of myotubes.</p></div> cell fusion;Erv 3 protein;PAX 7 gene regulations;biopsy;rxr;ERV envelope proteins;muscle biopsies;syncytin;Cellular receptors SLC 1A;SC nuclei;myoblast cell cultures;Other cell fusion events;Fusogenic Endogenous Retroviral Genes;SLC 1A protein expression;bone resorbing osteoclasts;ppar;myofiber;envelope genes 2015-07-08
    https://plos.figshare.com/articles/dataset/Long_Term_Endurance_Exercise_in_Humans_Stimulates_Cell_Fusion_of_Myoblasts_along_with_Fusogenic_Endogenous_Retroviral_Genes_In_Vivo_/1477108
10.1371/journal.pone.0132099