Autocrine and immune cell-derived BDNF in human skeletal muscle: Implications for myogenesis and tissue regeneration

Emanuela Colombo, Francesco Bedogni, Isabella Lorenzetti, Nicoletta Landsberger, Stefano C. Previtali, Cinthia Farina

Research output: Contribution to journalArticle

Abstract

The neurotrophin system has a role in skeletal muscle biology. Conditional depletion of BDNF in mouse muscle precursor cells alters myogenesis and regeneration in vivo. However, the expression, localization and function of BDNF in human skeletal muscle tissue is not known, so the relevance of the rodent findings for human muscle are unknown. Here we address this by combining ex vivo histological investigations on human biopsies with in vitro analyses of human primary myocytes. We found that BDNF was expressed by precursor and differentiated cells both in vitro and in vivo. Differential analysis of BDNF receptors showed expression of p75NTR and not of TrkB in myocytes, suggesting that the BDNF-p75NTR axis is predominant in human skeletal muscle cells. Several in vitro functional experiments demonstrated that BDNF gene silencing or protein blockade in myoblast cultures hampered myogenesis. Finally, histological investigations of inflammatory myopathy biopsies revealed that infiltrating immune cells localized preferentially near p75NTR-positive regenerating fibres and that they produced BDNF. In conclusion, BDNF is an autocrine factor for skeletal muscle cells and may regulate human myogenesis. Furthermore, the preferential localization of BDNF-producing immune cells near p75NTR-positive regenerating myofibres suggests that immune cell-derived BDNF may sustain tissue repair in inflamed muscle.

Original languageEnglish
Pages (from-to)190-198
Number of pages9
JournalJournal of Pathology
Volume231
Issue number2
DOIs
Publication statusPublished - Oct 2013

Keywords

  • BDNF
  • human skeletal muscle
  • immune cells
  • inflammation
  • myogenesis
  • neurotrophin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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