Journal of Muscle Research & Cell Motility

, Volume 22, Issue 8, pp 627–633

Content and localization of myostatin in mouse skeletal muscles during aging, mechanical unloading and reloading

  • Shigeo Kawada
  • Chikashi Tachi
  • Naokata Ishii


Changes in myostatin content and localization in mouse skeletal muscles were investigated during aging, hindlimb suspension (HS) and reloading after HS. During aging, the content of myostatin among solubilized proteins in gastrocnemius and plantaris muscles (Gast/Plant) was initially low and increased until their wet weight/body weight ratio reached a peak. It remained unchanged with further aging, although gradual atrophy of the muscles was seen to occur. Also, the myostatin content did not change significantly during HS (up to 14 days) in both Gast/Plant and soleus muscles, though the muscles showed morphological signs of atrophy. However, reloading for 2 days after a 14-day HS caused significant decreases in the myostatin content in both of these muscles. Immunohistochemical observations showed the sarcoplasmic existence of myostatin, the amount of which appeared to decrease after reloading. The results suggest that myostatin plays a part in the processes of muscular growth and loading-induced hypertrophy, but is not involved in either aging-related or unloading-induced muscular atrophy.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Akiyoshi S, Inoue H, Hanai J, Kusanagi K, Nemoto N, Miyazono K and Kawabata M (1999) c-Ski acts as a transcriptional corepressor in transforming growth factor-β signaling through interaction with Smads. J Biol Chem 274(49): 35,269–35,277.CrossRefGoogle Scholar
  2. Cadavid NFG, Taylor WE, Yarasheski K, Hikim IS, Ma K, Ezzat S, Shen R, Lalani R, Asa S, Mamita M, Nair G, Arver S and Bhasin S (1998) Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc Natl Acad Sci USA 95: 14,938–14,943.Google Scholar
  3. Carlson CJ, Booth FW and Gordon SE (1999) Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading. Am J Physiol 277: R601–R606.PubMedGoogle Scholar
  4. Daopin S, Piez KA, Ogawa Y and Davies DR (1992) Crystal structure of transforming growth factor-β2: an unusual fold for the superfamily. Science 257: 369–372.PubMedGoogle Scholar
  5. Elisabeth R, Davis B, Shoturma DI, Musaro A, Rosenthal N and Sweeney HL (1998) Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function. Proc Natl Acad Sci USA 95: 15,603–15,607.Google Scholar
  6. Ferrell ER, Conte V, Lawrence EC, Roth SM, Hagberg JM and Hurley BF (1999) Frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes. Genomics 62: 203–207.PubMedCrossRefGoogle Scholar
  7. Florini J, Ewton D and Roof S (1991) Insulin-like growth factor-I stimulates terminal myogenic differentiation by induction of myogenin gene expression. Mol Endocrinol 5: 718–724.PubMedCrossRefGoogle Scholar
  8. Floss T, Arnold HH and Braun T (1997) A role for FGF-6 in skeletal muscle regeneration. Genes Dev 11: 2040–2051.PubMedGoogle Scholar
  9. Goldspink G (1999) Changes in muscle mass and phenotype and the expression of autocrine and systemic growth factors by muscle in response to stretch and overload. J Anat 194: 323–334.PubMedCrossRefGoogle Scholar
  10. Grobet L, Martin LJR, Poncelet D, Pirottin D, Brouwers B, Riquet J, Schoeberlein A, Dunner S, Ménissier F, Massabanda J, Fries R, Hanset R and Georges M (1997) A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nature Genet 17: 71–74.PubMedCrossRefGoogle Scholar
  11. Henneman E and Mendell LM (1981) Functional organization of motoneurone pool and its inputs. In: Brooks VB (ed.). Handbook of Physiology. The Nervous System, Section 1. (vol. II, pp. 423) American Physiol. Soc., Bethasda, MD.Google Scholar
  12. Hikida RS, Nostran SV, Murray JD, Staron RS, Gordon S and Kraemer WJ (1997) Myonuclear loss in atrophied soleus muscle fibers. Anat Rec 247: 350–354.PubMedCrossRefGoogle Scholar
  13. Joubert Y and Tobin C (1989) Satellite cell proliferation and increase in the number of myonuclei induced by testosterone in the levator ani muscle of the adult female rat. Dev Biol 131(2): 550–557.PubMedGoogle Scholar
  14. Kirk S, Oldham J, Kambadur R, Sharma M, Dobbie P and Bass J (2000) Myostatin regulation during skeletal muscle regeneration. J Cell Physiol 184: 356–363.PubMedCrossRefGoogle Scholar
  15. Kretzschmar M, Doody J, Timokhina I and Massagué J (1999) A mechanism of repression of TGFβ/Smad signaling by oncogenic Ras. Genes Dev 13: 804–816.PubMedGoogle Scholar
  16. Li H and Capetanaki Y (1994) An E box in the desmin promoter cooperates with the E box and MEF-2 sites of a distal enhancer to direct muscle-specific transcription. EMBO J 13: 3580–3589.PubMedGoogle Scholar
  17. Mason AJ, Farnworth PG and Sullivan J (1996) Characterization and determination of the biological activities of noncleavable high molecular weight forms of inhibin A and activin A. Mol Endocrinol 10: 1055–1065.PubMedCrossRefGoogle Scholar
  18. McPherron AC, Lawler AM and Lee SJ (1997) Regulation of skeletal muscle mass in mice by a new TGF-β superfamily member. Nature 387: 83–90.PubMedCrossRefGoogle Scholar
  19. McPherron AC and Lee SJ (1997) Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci USA 94: 12457–12461.PubMedCrossRefGoogle Scholar
  20. Miyazono K (2000) TGF-β signaling by Smad proteins. Cytokine Growth Factor Rev 11: 15–22.PubMedCrossRefGoogle Scholar
  21. Miyazono K (2001) TGF-β/Smad signaling. Protein, Nucleic Acid and Enzyme, Japan 46(2): 105–110.Google Scholar
  22. Morey-Holten E and Wronski TJ (1981) Animal models for simulating weightlessness. Physiologist 24: S45–48Google Scholar
  23. Nakashima M, Toyono T, Akamine A and Joyner A (1999) Expression of growth/differentiation factor 11, a new member of the BMP/TGFβ superfamily during mouse embryogenesis. Mech Dev 80: 185–189.PubMedCrossRefGoogle Scholar
  24. Sakuma K, Watanabe K, Sano M, Uramoto I and Totsuka T (2000) Differential adaptation of growth and differentiation factor 8/myostatin, fibroblast growth factor 6 and leukemia inhibitory factor in overloaded, regenerating and denervated rat muscles. Biochim Biophys Acta 1497: 77–88.PubMedCrossRefGoogle Scholar
  25. Schlunegger M and Grütter MG (1992) An unusual feature revealed by the crystal structure at 2.2 Å resolution of human transforming growth factor-β2. Nature 358: 430–434PubMedCrossRefGoogle Scholar
  26. Schultz E (1989) Satellite cell behavior during skeletal muscle growth and regeneration. Med Sci Sport Exerc 21: S181–S186.Google Scholar
  27. Shaoquan J, Losinski RL, Cornelius SG, Frank GR, Willis GM, Gerrard DE, Depreux FFS and Spurlock ME (1998) Myostatin expression in porcine tissue: tissue specificity and developmental and postnatal regulation. Am J Physiol 275: R1265–R1273.Google Scholar
  28. Wehling M, Cai B and Tidball JG (2000) Modulation of myostatin expression during modified muscle use. FASEB J 14: 103–110.PubMedGoogle Scholar
  29. Wotton D, Lo SR, Lee S and Massagué J (1999) A Smad transcriptional corepressor. Cell 97: 29–39.PubMedCrossRefGoogle Scholar
  30. Zhu X, Hadhazy M, Wehling M, Tidball JG and NcNally EM (2000) Dominant negative myostatin produces hypertrophy without hyperplasia in muscle. FEBS Lett 474: 71–75.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Shigeo Kawada
    • 1
  • Chikashi Tachi
    • 2
  • Naokata Ishii
    • 1
  1. 1.Department of Life Sciences, Graduate School of Arts and SciencesThe University of TokyoTokyoJapan
  2. 2.Laboratory of Developmental and Reproductive Biotechnology, Department of Animal Resource Sciences, School of Veterinary Medicine and Life SciencesAzabu UniversityKanagawaJapan

Personalised recommendations