Brain-derived Neurotrophic Factor Regulates Satellite Cell Differentiation and Skeltal Muscle Regeneration
Open Access
- 1 July 2010
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 21 (13), 2182-2190
- https://doi.org/10.1091/mbc.e10-02-0154
Abstract
In adult skeletal muscle, brain-derived neurotrophic factor (BDNF) is expressed in myogenic progenitors known as satellite cells. To functionally address the role of BDNF in muscle satellite cells and regeneration in vivo, we generated a mouse in which BDNF is specifically depleted from skeletal muscle cells. For comparative purposes, and to determine the specific role of muscle-derived BDNF, we also examined muscles of the complete BDNF−/−mouse. In both models, expression of the satellite cell marker Pax7 was significantly decreased. Furthermore, proliferation and differentiation of primary myoblasts was abnormal, exhibiting delayed induction of several markers of differentiation as well as decreased myotube size. Treatment with exogenous BDNF protein was sufficient to rescue normal gene expression and myotube size. Because satellite cells are responsible for postnatal growth and repair of skeletal muscle, we next examined whether regenerative capacity was compromised. After injury, BDNF-depleted muscle showed delayed expression of several molecular markers of regeneration, as well as delayed appearance of newly regenerated fibers. Recovery of wild-type BDNF levels was sufficient to restore normal regeneration. Together, these findings suggest that BDNF plays an important role in regulating satellite cell function and regeneration in vivo, particularly during early stages.Keywords
This publication has 45 references indexed in Scilit:
- The Low-Affinity Receptor for Neurotrophins p75NTR Plays a Key Role for Satellite Cell Function in Muscle Repair Acting via RhoAMolecular Biology of the Cell, 2009
- Asymmetric Self-Renewal and Commitment of Satellite Stem Cells in MuscleCell, 2007
- Brain-Derived Neurotrophic Factor: A Newly Described Mediator of AngiogenesisTrends in Cardiovascular Medicine, 2007
- Neurotrophin-regulated signalling pathwaysPhilosophical Transactions B, 2006
- BDNF Is Expressed in Skeletal Muscle Satellite Cells and Inhibits Myogenic DifferentiationJournal of Neuroscience, 2006
- Inflammatory processes in muscle injury and repairAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2005
- The protean actions of neurotrophins and their receptors on the life and death of neuronsTrends in Neurosciences, 2005
- BDNF rescues myosin heavy chain IIB muscle fibers after neonatal nerve injuryAmerican Journal of Physiology-Cell Physiology, 2004
- Activated Human T Cells, B Cells, and Monocytes Produce Brain-derived Neurotrophic Factor In Vitro and in Inflammatory Brain Lesions: A Neuroprotective Role of Inflammation?The Journal of Experimental Medicine, 1999
- Membrane-active polypeptides from snake venom: Cardiotoxins and haemocytotoxinsCellular and Molecular Life Sciences, 1974