Satellite cells and utrophin are not directly correlated with the degree of skeletal muscle damage in mdx mice

Abstract

Yamane, Akira, Satonari Akutsu, Thomas G. H. Diekwisch, and Ryoichi Matsuda. Satellite cells and utrophin are not directly correlated with the degree of skeletal muscle damage in mdx mice. Am J Physiol Cell Physiol 289: C42-C48, 2005. First published February 9, 2005 doi:10.1152/ajpcell.00577.2004.-To determine whether muscle satellite cells and utrophin are correlated with the degree of damage in mdx skeletal muscles, we measured the area of the degenerative region as an indicator of myofiber degeneration in the masseter, gastrocnemius, soleus, and diaphragm muscles of mdx mice. Furthermore, we analyzed the expression levels of the paired box homeotic gene 7 (pax7), m-cadherin (the makers of muscle satellite cells), and utrophin mRNA. We also investigated the immunolocalization of m-cadherin and utrophin proteins in the muscles of normal C57BL/10J (B10) and mdx mice. The expression level of pax7 mRNA and the percentage of m-cadherin-positive cells among the total number of cell nuclei in the muscle tissues in all four muscles studied were greater in the mdx mice than in the B10 mice. However, there was no significant correlation between muscle damage and expression level for pax7 mRNA (R ϭ Ϫ0.140), nor was there a correlation between muscle damage and the percentage of satellite cells among the total number of cell nuclei (R ϭ Ϫ0.411) in the mdx mice. The expression level of utrophin mRNA and the intensity of immunostaining for utrophin in all four muscles studied were greater in the mdx mice than in the B10 mice. However, there also was not a significant correlation between muscle damage and expression level of utrophin mRNA (R ϭ 0.231) in the mdx mice, although upregulated utrophin was incorporated into the sarcolemma. These results suggest that satellite cells and utrophin are not directly correlated with the degree of skeletal muscle damage in mdx mice. dystrophy; pax7; m-cadherin; dystrophin-related proteins THE X CHROMOSOME-LINKED MUSCULAR dystrophic mdx mouse lacks the sarcolemmal protein dystrophin and represents a genetic homolog of human Duchenne muscular dystrophy. Dystrophin is a 427-kDa cytoskeletal protein that is expressed in the sarcolemma (the membrane structure of the myofiber) and contributes to the stability of the sarcolemma. Lack of dystrophin causes myofiber degeneration caused by membrane damage, Ca 2ϩ overuptake by muscle cells, muscle overcontraction, and activation of intracellular proteinase (2, 8). The damage to myofibers varies among the muscles of the mdx mouse; the mdx diaphragm muscle is damaged more severely by dystrophy than are the other muscles (10, 27), whereas craniofacial muscles such as the masseter and extraocular muscles are less damaged (16,20). However, the mechanism underlying differences in the degree of myofiber damage among mdx skeletal muscles is unclear.Muscle satellite cells are mononucleated, quiescent stem cells that reside between the sarcolemma and the basal lamina of adult myofibers (4, 13). In response to stimuli such as mechanical loading, unloading, d...

Postnatal overexpression of the CT GalNAc transferase inhibits muscular dystrophy in mdx mice without altering muscle growth or neuromuscular development: Evidence for a utrophin-independent mechanism

“…Utrophin upregulation does occur in some mdx myofibers, particularly in regenerating myofibers in younger mdx animals [3,35,36]. Indeed, some of our early experiments with AAV2-Galgt2, which yielded far fewer infected myofibers on a vg basis than our later experiments with AAV1-Galgt2, showed that some utrophin upregulation did occur in some Galgt2 overexpressing myofibers.…”

Are Human and Mouse Satellite Cells Really the Same?

“…Numbers of M-cadherin1 satellite cells (calculated as the ratio of M-cadherin1 cells/total cell nuclei) were greater in mdx than in C57Bl/10 mouse muscles (Yamane et al 2005), but their activation state was not determined. There is evidence that satellite cells in muscles of DMD patients may be in a more activated state (Wakayama et al 1979;Watkins and Cullen 1988;Maier and Bornemann 1999), as they seem to be in mdx muscles (Bhagavati et al 1996;Ikemoto et al 2007) and be detrimentally influenced by the pathological environment (Watkins and Cullen 1986).…”

Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation

“…The role of myofibre regeneration, and therefore the role of satellite cells, in the pathogenesis of DMD is debated. Firstly, it is controversial whether satellite cell numbers are altered in dystrophic muscle 9 10 11 12 13 14 . Secondly, it is controversial whether satellite cells in dystrophic muscle are directly impaired and participate in muscular dystrophy pathogenesis by impairing myofibre regeneration or whether satellite cells simply become exhausted by the continuous cycles of degeneration/regeneration without being intrinsically impaired 12 15 16 17 18 19 20 .…”