Long-Term Endurance Exercise in Humans Stimulates Cell Fusion of Myoblasts along with Fusogenic Endogenous Retroviral Genes In Vivo

Journal article

Publication Details

Author(s): Frese S, Rübner M, Suhr F, Konou TM, Tappe KA, Toigo M, Jung HH, Henke C, Steigleder R, Strissel P, Hübner H, Beckmann M, van der Keylen P, Schoser B, Schiffer T, Frese L, Bloch W, Strick R
Journal: PLoS ONE
Publication year: 2015
Volume: 10
Journal issue: 7
Pages range: e0132099
ISSN: 1932-6203


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 Syncytin-1 and Syncytin-3, but also for the non-fusogenic erv3. Immunohistochemistry analyses showed that Syncytin-1 mainly localized to the sarcolemma of myofibers positive for myosin heavy-chain isotypes. Cellular receptors SLC1A4 and SLC1A5 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, PPAR? and RXR?, showed no protein expression in the myofiber, whereas the pCREB-Ser133 activator of Syncytin-1 was enriched to SC nuclei and myonuclei. Syncytin-1, Syncytin-3, SLC1A4 and PAX7 gene regulations along with MyoD1 and myogenin 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.

FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Henke, Christine
Hübner, Hanna Dr. rer. nat.
Professur für Experimentelle Tumorpathologie
Rübner, Matthias PD Dr.
Strick, Reiner Prof. Dr.
Medizinische Fakultät
Strissel, Pamela PD Dr.
Medizinische Fakultät
van der Keylen, Piet Dr. rer. biol. hum.
Lehrstuhl für Anatomie und Zellbiologie

External institutions with authors

Deutsche Sporthochschule Köln
Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich
Ludwig-Maximilians-Universität (LMU)
Universitätsspital Zürich (USZ)
Universität Zürich (UZH)

How to cite

Frese, S., Rübner, M., Suhr, F., Konou, T.M., Tappe, K.A., Toigo, M.,... Strick, R. (2015). Long-Term Endurance Exercise in Humans Stimulates Cell Fusion of Myoblasts along with Fusogenic Endogenous Retroviral Genes In Vivo. PLoS ONE, 10(7), e0132099. https://dx.doi.org/10.1371/journal.pone.0132099

Frese, Sebastian, et al. "Long-Term Endurance Exercise in Humans Stimulates Cell Fusion of Myoblasts along with Fusogenic Endogenous Retroviral Genes In Vivo." PLoS ONE 10.7 (2015): e0132099.


Last updated on 2018-09-10 at 07:19