Display options
Cite
Uemura K, Hayashi M, Itsubo T, et al. Myostatin promotes tenogenic differentiation of C2C12 myoblast cells through Smad3. FEBS Open Bio. 2017;7(4):522-532doi: 10.1002/2211-5463.12200.
Uemura, K., Hayashi, M., Itsubo, T., Oishi, A., Iwakawa, H., Komatsu, M., Uchiyama, S., & Kato, H. (2017). Myostatin promotes tenogenic differentiation of C2C12 myoblast cells through Smad3. FEBS open bio, 7(4), 522-532. https://doi.org/10.1002/2211-5463.12200
Uemura, Kazutaka, et al. "Myostatin promotes tenogenic differentiation of C2C12 myoblast cells through Smad3." FEBS open bio vol. 7,4 (2017): 522-532. doi: https://doi.org/10.1002/2211-5463.12200
Uemura K, Hayashi M, Itsubo T, Oishi A, Iwakawa H, Komatsu M, Uchiyama S, Kato H. Myostatin promotes tenogenic differentiation of C2C12 myoblast cells through Smad3. FEBS Open Bio. 2017 Feb 20;7(4):522-532. doi: 10.1002/2211-5463.12200. eCollection 2017 Apr. PMID: 28396837; PMCID: PMC5377394.
Copy Download .nbib Format: NLM
Share it on

FEBS Open Bio. 2017 Feb 20;7(4):522-532. doi: 10.1002/2211-5463.12200. eCollection 2017 Apr.

Myostatin promotes tenogenic differentiation of C2C12 myoblast cells through Smad3.

FEBS open bio

Kazutaka Uemura, Masanori Hayashi, Toshiro Itsubo, Ayumu Oishi, Hiroko Iwakawa, Masatoshi Komatsu, Shigeharu Uchiyama, Hiroyuki Kato

Affiliations

  1. Department of Orthopaedic Surgery Shinshu University School of Medicine Matsumoto Japan.
  2. Sports Medicine Center Aizawa Hospital Matsumoto Japan.

PMID: 28396837 PMCID: PMC5377394 DOI: 10.1002/2211-5463.12200

Abstract

Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, is expressed in developing and adult skeletal muscle and negatively regulates skeletal muscle growth. Recently, myostatin has been found to be expressed in tendons and increases tendon fibroblast proliferation and the expression of tenocyte markers. C2C12 is a mouse myoblast cell line, which has the ability to transdifferentiate into osteoblast and adipocyte lineages. We hypothesized that myostatin is capable of inducing tenogenic differentiation of C2C12 cells. We found that the expression of scleraxis, a tendon progenitor cell marker, is much higher in C2C12 than in the multipotent mouse mesenchymal fibroblast cell line C3H10T1/2. In comparison with other growth factors, myostatin significantly up-regulated the expression of the tenogenic marker in C2C12 cells under serum-free culture conditions. Immunohistochemistry showed that myostatin inhibited myotube formation and promoted the formation of spindle-shaped cells expressing tenomodulin. We examined signaling pathways essential for tenogenic differentiation to clarify the mechanism of myostatin-induced differentiation of C2C12 into tenocytes. The expression of tenomodulin was significantly suppressed by treatment with the ALK inhibitor SB341542, in contrast to p38MAPK (SB203580) and MEK1 (PD98059) inhibitors. RNAi silencing of Smad3 significantly suppressed myostatin-induced tenomodulin expression. These results indicate that myostatin has a potential role in the induction of tenogenic differentiation of C2C12 cells, which have tendon progenitor cell characteristics, through activation of Smad3-mediated signaling.

Keywords: C2C12; Smad3; myostatin; tenocyte; tenomodulin

References

  1. J Cell Sci. 1998 Mar;111 ( Pt 6):769-79 - PubMed
  2. J Cell Biochem. 1997 Oct 1;67(1):66-74 - PubMed
  3. J Hand Surg Am. 2014 Sep;39(9):1706-13 - PubMed
  4. Development. 2009 Apr;136(8):1351-61 - PubMed
  5. Biomaterials. 2011 Nov;32(32):8097-107 - PubMed
  6. J Orthop Res. 2006 Apr;24(4):831-41 - PubMed
  7. J Biol Chem. 2011 Feb 18;286(7):5855-67 - PubMed
  8. J Biol Chem. 1992 May 5;267(13):9059-64 - PubMed
  9. J Cell Biol. 2000 Dec 11;151(6):1221-34 - PubMed
  10. J Orthop Res. 2001 Nov;19(6):1199-202 - PubMed
  11. Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):388-93 - PubMed
  12. Endocrinology. 2014 Mar;155(3):670-5 - PubMed
  13. Cell Res. 2011 Nov;21(11):1591-604 - PubMed
  14. Mol Cell Biol. 2003 Oct;23(20):7230-42 - PubMed
  15. J Orthop Res. 2012 Nov;30(11):1710-8 - PubMed
  16. J Orthop Res. 2003 Sep;21(5):826-35 - PubMed
  17. Dev Biol. 2002 Nov 15;251(2):241-57 - PubMed
  18. J Clin Invest. 2013 Aug;123(8):3564-76 - PubMed
  19. J Appl Physiol (1985). 2007 Feb;102(2):573-81 - PubMed
  20. Sci Transl Med. 2016 Jul 20;8(348):348ra98 - PubMed
  21. Nature. 1977 Dec 22-29;270(5639):725-7 - PubMed
  22. Nat Biotechnol. 2016 May 6;34(5):458-61 - PubMed
  23. Growth Factors. 2009 Aug;27(4):247-54 - PubMed
  24. Biochem Biophys Res Commun. 2000 Apr 13;270(2):510-6 - PubMed
  25. Endocrinology. 2016 Jan;157(1):282-91 - PubMed
  26. Cell. 2003 Apr 18;113(2):235-48 - PubMed
  27. J Biol Chem. 2007 Aug 31;282(35):25852-63 - PubMed
  28. Development. 2001 Oct;128(19):3855-66 - PubMed
  29. Cell Mol Life Sci. 2014 Nov;71(22):4361-71 - PubMed
  30. J Biol Chem. 2008 Jul 11;283(28):19371-8 - PubMed
  31. Am J Physiol Regul Integr Comp Physiol. 2012 May;302(9):R1059-66 - PubMed
  32. J Endocrinol. 2012 Oct;215(1):177-87 - PubMed
  33. Biochem Biophys Res Commun. 2001 Mar 9;281(4):902-6 - PubMed
  34. Exp Cell Res. 2004 Mar 10;294(1):254-68 - PubMed
  35. Nat Med. 2007 Oct;13(10 ):1219-27 - PubMed
  36. Tissue Eng Part A. 2010 Sep;16(9):2941-51 - PubMed
  37. J Biol Chem. 1995 Nov 24;270(47):28183-7 - PubMed
  38. Endocrinology. 2005 Aug;146(8):3547-57 - PubMed
  39. Dev Biol. 2006 Oct 1;298(1):234-47 - PubMed
  40. Cell Signal. 2011 Sep;23(9):1441-6 - PubMed
  41. J Cell Physiol. 2002 Feb;190(2):170-9 - PubMed
  42. Nature. 1997 May 1;387(6628):83-90 - PubMed
  43. Anat Rec (Hoboken). 2009 Mar;292(3):396-400 - PubMed
  44. Nature. 1997 Oct 9;389(6651):631-5 - PubMed
  45. J Biol Chem. 2002 Dec 20;277(51):49831-40 - PubMed
  46. Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10538-42 - PubMed
  47. Am J Physiol Cell Physiol. 2006 Sep;291(3):C538-45 - PubMed
  48. Endocr Rev. 2002 Dec;23(6):787-823 - PubMed
  49. J Cell Biol. 1994 Dec;127(6 Pt 1):1755-66 - PubMed
  50. J Orthop Res. 2013 Sep;31(9):1475-83 - PubMed
  51. Stem Cells. 2015 Feb;33(2):443-55 - PubMed
  52. Wound Repair Regen. 2008 May-Jun;16(3):399-407 - PubMed
  53. Cell Signal. 2005 Mar;17 (3):365-75 - PubMed
  54. Cell. 1983 Apr;32(4):1171-80 - PubMed
  55. J Cell Biol. 1998 Jan 12;140(1):111-8 - PubMed
  56. Genes Dev. 2008 Mar 1;22(5):668-81 - PubMed
  57. J Appl Physiol (1985). 2009 Jan;106(1):178-86 - PubMed

Publication Types