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


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Abstract

The neurotrophin system has a role in skeletal muscle biology. Conditional depletion of BDNF in mouse muscle precursor cells alters myogenesis and regenerationin 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 combiningex vivohistological investigations on human biopsies within vitroanalyses of human primary myocytes. We found that BDNF was expressed by precursor and differentiated cells bothin vitroandin 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. Severalin vitrofunctional experiments demonstrated thatBDNFgene 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. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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