Judy E. Anderson*
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0W3
Muscle satellite cells are quiescent precursors interposed between myofibers and a sheath of external lamina. Although their
activation and recruitment to cycle enable muscle repair and adaptation,
the activation signal is not known. Evidence is presented that
nitric oxide (NO) mediates satellite cell activation, including
morphological hypertrophy and decreased adhesion in the fiber-lamina
complex. Activation in vivo occurred within 1 min after injury.
Cell isolation and histology showed that pharmacological inhibition
of nitric oxide synthase (NOS) activity prevented the immediate
injury-induced myogenic cell release and delayed the hypertrophy
of satellite cells in that muscle. Transient activation of satellite
cells in contralateral muscles 10 min later suggested that a circulating
factor may interact with NO-mediated signaling. Interestingly,
satellite cell activation in muscles of
mdx dystrophic mice and
NOS-I knockout mice quantitatively resembled NOS-inhibited release
of normal cells, in agreement with reports of displaced and reduced
NOS expression in dystrophin-deficient
mdx muscle and the complete
loss of NOS-I expression in knockout mice. Brief NOS inhibition
in normal and
mdx mice during injury produced subtle alterations
in subsequent repair, including apoptosis in myotube nuclei and
myotube formation inside laminar sheaths. Longer NOS inhibition
delayed and restricted the extent of repair and resulted in fiber
branching. A model proposes the hypothesis that NO release mediates
satellite cell activation, possibly via shear-induced rapid increases
in NOS activity that produce “NO
transients.”
Anderson, J. E. (2000). A role for nitric oxide in muscle repair: nitric oxide-mediated activation of muscle satellite cells. Mol. Biol. Cell. 11, 1859-1874.[Abstract]
