Identification and validation of novel contraction-regulated myokines released from primary human skeletal muscle cells

PLoS One. 2013 Apr 24;8(4):e62008. doi: 10.1371/journal.pone.0062008. Print 2013.


Proteins secreted by skeletal muscle, so called myokines, have been shown to affect muscle physiology and additionally exert systemic effects on other tissues and organs. Although recent profiling studies have identified numerous myokines, the amount of overlap from these studies indicates that the secretome of skeletal muscle is still incompletely characterized. One limitation of the models used is the lack of contraction, a central characteristic of muscle cells. Here we aimed to characterize the secretome of primary human myotubes by cytokine antibody arrays and to identify myokines regulated by contraction, which was induced by electrical pulse stimulation (EPS). In this study, we validated the regulation and release of two selected myokines, namely pigment epithelium derived factor (PEDF) and dipeptidyl peptidase 4 (DPP4), which were recently described as adipokines. This study reveals that both factors, DPP4 and PEDF, are secreted by primary human myotubes. PEDF is a contraction-regulated myokine, although PEDF serum levels from healthy young men decrease after 60 min cycling at VO2max of 70%. Most interestingly, we identified 52 novel myokines which have not been described before to be secreted by skeletal muscle cells. For 48 myokines we show that their release is regulated by contractile activity. This profiling study of the human skeletal muscle secretome expands the number of myokines, identifies novel contraction-regulated myokines and underlines the overlap between proteins which are adipokines as well as myokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / metabolism
  • Adolescent
  • Adult
  • Dipeptidyl Peptidase 4 / blood
  • Dipeptidyl Peptidase 4 / metabolism
  • Eye Proteins / blood
  • Eye Proteins / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle Cells / metabolism*
  • Muscle Contraction / physiology*
  • Muscle Proteins / blood
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / metabolism*
  • Nerve Growth Factors / blood
  • Nerve Growth Factors / metabolism
  • Protein Array Analysis
  • Serpins / blood
  • Serpins / metabolism
  • Young Adult


  • Adipokines
  • Eye Proteins
  • Muscle Proteins
  • Nerve Growth Factors
  • Serpins
  • pigment epithelium-derived factor
  • Dipeptidyl Peptidase 4

Grant support

This work was supported by the Ministerium für Wissenschaft und Forschung des Landes Nordrhein-Westfalen (Ministry of Science and Research of the State of North Rhine-Westphalia), the Bundesministerium für Gesundheit (Federal Ministry of Health), the Commission of the European Communities (Collaborative Project ADAPT, contract number HEALTH-F2-2008-201100), and the Deutsche Forschungsgemeinschaft (EC 440/1-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.