Title | Sca-1-expressing nonmyogenic cells contribute to fibrosis in aged skeletal muscle. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Hidestrand M, Richards-Malcolm S, Gurley CM, Nolen G, Grimes B, Waterstrat A, Van Zant G, Peterson CA |
Journal | J Gerontol A Biol Sci Med Sci |
Volume | 63 |
Issue | 6 |
Pagination | 566-79 |
Date Published | 2008 Jun |
ISSN | 1079-5006 |
Keywords | Aging, Animals, Antigens, Ly, Cells, Cultured, Female, Fibrosis, Leukocyte Common Antigens, Membrane Proteins, Mice, Mice, Inbred DBA, Muscle, Skeletal, MyoD Protein, Regeneration |
Abstract | We report an age-dependent increase in nonimmunohematopoietic cells (CD45neg) in regenerating muscle characterized by high stem-cell antigen (Sca-1) expression. In aged regenerating muscle, only 14% of these CD45negSca-1pos cells express MyoD, whereas 82% of CD45negSca-1(pos) cells are MyoDpos in young adult muscle. In vitro, CD45negMyoDnegSca-1pos cells overexpress fibrosis-promoting genes, potentially controlled by Wnt2. The cells are proliferative, nonmyogenic, and nonadipogenic, and arise in clonally derived myoblast cultures from aged mice. MyoDneg Sca-1pos nonmyogenic cells also emerge in C2C12 myoblast cultures at late passage. Both in vitro and in vivo studies suggest that MyoDnegSca-1pos cells from aged muscle are more susceptible to apoptosis than myoblasts, which may contribute to depletion of the satellite cell pool. Thus, with age, a subset of myoblasts takes on an altered phenotype, which is marked by high Sca-1 expression. These cells do not participate in muscle regeneration, and instead may contribute to muscle fibrosis in aged muscle. |
DOI | 10.1093/gerona/63.6.566 |
Alternate Journal | J. Gerontol. A Biol. Sci. Med. Sci. |
PubMed ID | 18559630 |
PubMed Central ID | PMC2755567 |
Grant List | AG20941 / AG / NIA NIH HHS / United States AG12411 / AG / NIA NIH HHS / United States R01 AG020941-05 / AG / NIA NIH HHS / United States P01 AG012411 / AG / NIA NIH HHS / United States R01 AG020941 / AG / NIA NIH HHS / United States P20 RR-16460 / RR / NCRR NIH HHS / United States P20 RR016460 / RR / NCRR NIH HHS / United States |