Cell and Tissue Research

, Volume 340, Issue 3, pp 541–548 | Cite as

Elevated satellite cell number in Duchenne muscular dystrophy

Regular Article

Abstract

The regenerative potential of muscle tissue relies mostly on satellite cells situated between the muscular basal membrane and the sarcolemma. The regeneration of muscle tissue comprises proliferation, the propagation of satellite cells, and their subsequent differentiation with the expression of multiple muscle-specific proteins. However, in Duchenne muscular dystrophy (DMD), regeneration cannot compensate for the loss of muscle tissue. To examine the regenerative potential in DMD, satellite cell nuclei number and markers of differentiation in DMD muscle from various disease states were compared with control muscle. Differentiation of satellite cells is characterized by the helix-loop-helix factor myogenin, which is never co-expressed with Pax7, whereas MyoD1 and Myf5 are co-expressed with Pax7, with Myf5 being present even in muscle of controls. The results indicate that satellite cell number is elevated in DMD in comparison with control muscle, even in advanced stages of dystrophy, suggesting that exhaustion of satellite cells is not the primary cause for failed regeneration. The expression of myogenin is correlated neither with fibrosis nor with age. We suggest variable factors influencing the differentiation of satellite cells in DMD.

Keywords

Duchenne muscular dystrophy Satellite cell Regeneration Proliferation Differentiation Human 

References

  1. Ates K, Yang SY, Orrell RW, Sinanan AC, Simons P, Solomon A, Beech S, Goldspink G, Lewis MP (2007) The IGF-I splice variant MGF increases progenitor cells in ALS, dystrophic, and normal muscle. FEBS Lett 581:2727–2732CrossRefPubMedGoogle Scholar
  2. Baxter RC (2000) Insulin-like growth factor (IGF)-binding proteins: interactions with IGFs and intrinsic bioactivities. Am J Physiol Endocrinol Metab 278:E967–E976PubMedGoogle Scholar
  3. Bernasconi P, Torchiana E, Confalonieri P, Brugnoni R, Barresi R, Mora M, Cornelio F, Morandi L, Mantegazza R (1995) Expression of transforming growth factor-beta 1 in dystrophic patient muscles correlates with fibrosis. Pathogenetic role of a fibrogenic cytokine. J Clin Invest 96:1137–1144CrossRefPubMedGoogle Scholar
  4. Bernasconi P, Di Blasi C, Mora M, Morandi L, Galbiati S, Confalonieri P, Cornelio F, Mantegazza R (1999) Transforming growth factor-beta1 and fibrosis in congenital muscular dystrophies. Neuromuscul Disord 9:28–33CrossRefPubMedGoogle Scholar
  5. Brennan TJ, Chakraborty T, Olson EN (1991) Mutagenesis of the myogenin basic region identifies an ancient protein motif critical for activation of myogenesis. Proc Natl Acad Sci USA 88:5675–5679CrossRefPubMedGoogle Scholar
  6. Bulman DE, Murphy EG, Zubrzycka-Gaarn EE, Worton RG, Ray PN (1991) Differentiation of Duchenne and Becker muscular dystrophy phenotypes with amino- and carboxy-terminal antisera specific for dystrophin. Am J Hum Genet 48:295–304PubMedGoogle Scholar
  7. Carlson BM, Faulkner JA (1989) Muscle transplantation between young and old rats: age of host determines recovery. Am J Physiol 256:C1262–C1266PubMedGoogle Scholar
  8. Cohn RD, Erp C van, Habashi JP, Soleimani AA, Klein EC, Lisi MT, Gamradt M, ap Rhys CM, Holm TM, Loeys BL, Ramirez F, Judge DP, Ward CW, Dietz HC (2007) Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states. Nat Med 13:204–210CrossRefPubMedGoogle Scholar
  9. Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433:760–764CrossRefPubMedGoogle Scholar
  10. Decary S, Hamida CB, Mouly V, Barbet JP, Hentati F, Butler-Browne GS (2000) Shorter telomeres in dystrophic muscle consistent with extensive regeneration in young children. Neuromuscul Disord 10:113–120CrossRefPubMedGoogle Scholar
  11. Deconinck N, Dan B (2007) Pathophysiology of Duchenne muscular dystrophy: current hypotheses. Pediatr Neurol 36:1–7CrossRefPubMedGoogle Scholar
  12. Delaporte C, Dehaupas M, Fardeau M (1984) Comparison between the growth pattern of cell cultures from normal and Duchenne dystrophy muscle. J Neurol Sci 64:149–160CrossRefPubMedGoogle Scholar
  13. Emery AE (1991) Population frequencies of inherited neuromuscular diseases—a world survey. Neuromuscul Disord 1:19–29CrossRefPubMedGoogle Scholar
  14. Hoffman EP, Brown RH Jr, Kunkel LM (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51:919–928CrossRefPubMedGoogle Scholar
  15. Iannaccone ST, Nagy B, Samaha FJ (1987) Decreased creatine kinase activity in cultured Duchenne dystrophic muscle cells. J Child Neurol 2:17–21CrossRefPubMedGoogle Scholar
  16. Ishimoto S, Goto I, Ohta M, Kuroiwa Y (1983) A quantitative study of the muscle satellite cells in various neuromuscular disorders. J Neurol Sci 62:303–314CrossRefPubMedGoogle Scholar
  17. Jasmin G, Tautu C, Vanasse M, Brochu P, Simoneau R (1984) Impaired muscle differentiation in explant cultures of Duchenne muscular dystrophy. Lab Invest 50:197–207PubMedGoogle Scholar
  18. Johnson BJ, White ME, Hathaway MR, Dayton WR (1999) Decreased steady-state insulin-like growth factor binding protein-3 (IGFBP-3) mRNA level is associated with differentiation of cultured porcine myogenic cells. J Cell Physiol 179:237–243CrossRefPubMedGoogle Scholar
  19. Li Y, Foster W, Deasy BM, Chan Y, Prisk V, Tang Y, Cummins J, Huard J (2004) Transforming growth factor-beta1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: a key event in muscle fibrogenesis. Am J Pathol 164:1007–1019PubMedGoogle Scholar
  20. Luz MA, Marques MJ, Santo NH (2002) Impaired regeneration of dystrophin-deficient muscle fibers is caused by exhaustion of myogenic cells. Braz J Med Biol Res 35:691–695CrossRefPubMedGoogle Scholar
  21. Maier F, Bornemann A (1999) Comparison of the muscle fiber diameter and satellite cell frequency in human muscle biopsies. Muscle Nerve 22:578–583CrossRefPubMedGoogle Scholar
  22. Marini JF, Pons F, Leger J, Loffreda N, Anoal M, Chevallay M, Fardeau M, Leger JJ (1991) Expression of myosin heavy chain isoforms in Duchenne muscular dystrophy patients and carriers. Neuromuscul Disord 1:397–409CrossRefPubMedGoogle Scholar
  23. Mauro A (1961) Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol 9:493–495CrossRefPubMedGoogle Scholar
  24. Megeney LA, Kablar B, Perry RL, Ying C, May L, Rudnicki MA (1999) Severe cardiomyopathy in mice lacking dystrophin and MyoD. Proc Natl Acad Sci USA 96:220–225CrossRefPubMedGoogle Scholar
  25. Nonaka I, Takagi A, Sugita H (1981) The significance of type 2C muscle fibers in Duchenne muscular dystrophy. Muscle Nerve 4:326–333CrossRefPubMedGoogle Scholar
  26. Oexle K, Zwirner A, Freudenberg K, Kohlschutter A, Speer A (1997) Examination of telomere lengths in muscle tissue casts doubt on replicative aging as cause of progression in Duchenne muscular dystrophy. Pediatr Res 42:226–231CrossRefPubMedGoogle Scholar
  27. Olive M, Martinez-Matos JA, Pirretas P, Povedano M, Navarro C, Ferrer I (1997) Expression of myogenic regulatory factors (MRFs) in human neuromuscular disorders. Neuropathol Appl Neurobiol 23:475–482CrossRefPubMedGoogle Scholar
  28. Pampusch MS, Hembree JR, Hathaway MR, Dayton WR (1990) Effect of transforming growth factor beta on proliferation of L6 and embryonic porcine myogenic cells. J Cell Physiol 143:524–528CrossRefPubMedGoogle Scholar
  29. Reimann J, Brimah K, Schroder R, Wernig A, Beauchamp JR, Partridge TA (2004) Pax7 distribution in human skeletal muscle biopsies and myogenic tissue cultures. Cell Tissue Res 315:233–242CrossRefPubMedGoogle Scholar
  30. Sabourin LA, Girgis-Gabardo A, Seale P, Asakura A, Rudnicki MA (1999) Reduced differentiation potential of primary MyoD-/- myogenic cells derived from adult skeletal muscle. J Cell Biol 144:631–643CrossRefPubMedGoogle Scholar
  31. Seale P, Sabourin LA, Girgis-Gabardo A, Mansouri A, Gruss P, Rudnicki MA (2000) Pax7 is required for the specification of myogenic satellite cells. Cell 102:777–786CrossRefPubMedGoogle Scholar
  32. Shefer G, Wleklinski-Lee M, Yablonka-Reuveni Z (2004) Skeletal muscle satellite cells can spontaneously enter an alternative mesenchymal pathway. J Cell Sci 117:5393–5404CrossRefPubMedGoogle Scholar
  33. Sherwood RI, Christensen JL, Conboy IM, Conboy MJ, Rando TA, Weissman IL, Wagers AJ (2004) Isolation of adult mouse myogenic progenitors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell 119:543–554CrossRefPubMedGoogle Scholar
  34. Shi X, Garry DJ (2006) Muscle stem cells in development, regeneration, and disease. Genes Dev 20:1692–1708CrossRefPubMedGoogle Scholar
  35. Sjogren K, Liu JL, Blad K, Skrtic S, Vidal O, Wallenius V, LeRoith D, Tornell J, Isaksson OG, Jansson JO, Ohlsson C (1999) Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci USA 96:7088–7092CrossRefPubMedGoogle Scholar
  36. Tajbakhsh S, Buckingham M (2000) The birth of muscle progenitor cells in the mouse: spatiotemporal considerations. Curr Top Dev Biol 48:225–268CrossRefPubMedGoogle Scholar
  37. Tajbakhsh S, Bober E, Babinet C, Pournin S, Arnold H, Buckingham M (1996) Gene targeting the myf-5 locus with nlacZ reveals expression of this myogenic factor in mature skeletal muscle fibres as well as early embryonic muscle. Dev Dyn 206:291–300CrossRefPubMedGoogle Scholar
  38. Vaidya TB, Rhodes SJ, Taparowsky EJ, Konieczny SF (1989) Fibroblast growth factor and transforming growth factor beta repress transcription of the myogenic regulatory gene MyoD1. Mol Cell Biol 9:3576–3579PubMedGoogle Scholar
  39. Wagers AJ, Conboy IM (2005) Cellular and molecular signatures of muscle regeneration: current concepts and controversies in adult myogenesis. Cell 122:659–667CrossRefPubMedGoogle Scholar
  40. Webster C, Blau HM (1990) Accelerated age-related decline in replicative life-span of Duchenne muscular dystrophy myoblasts: implications for cell and gene therapy. Somat Cell Mol Genet 16:557–565CrossRefPubMedGoogle Scholar
  41. Webster C, Silberstein L, Hays AP, Blau HM (1988) Fast muscle fibers are preferentially affected in Duchenne muscular dystrophy. Cell 52:503–513CrossRefPubMedGoogle Scholar
  42. White JD, Scaffidi A, Davies M, McGeachie J, Rudnicki MA, Grounds MD (2000) Myotube formation is delayed but not prevented in MyoD-deficient skeletal muscle: studies in regenerating whole muscle grafts of adult mice. J Histochem Cytochem 48:1531–1544PubMedGoogle Scholar
  43. Yablonka-Reuveni Z, Rivera AJ (1994) Temporal expression of regulatory and structural muscle proteins during myogenesis of satellite cells on isolated adult rat fibers. Dev Biol 164:588–603CrossRefPubMedGoogle Scholar
  44. Yablonka-Reuveni Z, Rudnicki MA, Rivera AJ, Primig M, Anderson JE, Natanson P (1999) The transition from proliferation to differentiation is delayed in satellite cells from mice lacking MyoD. Dev Biol 210:440–455CrossRefPubMedGoogle Scholar
  45. Young C, Lin MY, Wang PJ, Shen YZ (1994) Immunocytochemical studies on desmin and vimentin in neuromuscular disorders. J Formos Med Assoc 93:829–835PubMedGoogle Scholar
  46. Zacks SI, Sheff MF (1982) Age-related impeded regeneration of mouse minced anterior tibial muscle. Muscle Nerve 5:152–161CrossRefPubMedGoogle Scholar
  47. Zammit PS, Relaix F, Nagata Y, Ruiz AP, Collins CA, Partridge TA, Beauchamp JR (2006) Pax7 and myogenic progression in skeletal muscle satellite cells. J Cell Sci 119:1824–1832CrossRefPubMedGoogle Scholar
  48. Zhao P, Hoffman EP (2004) Embryonic myogenesis pathways in muscle regeneration. Dev Dyn 229:380–392CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Division of Neuropediatrics and Muscle DisordersUniversity Children’s Hospital FreiburgFreiburgGermany

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