骨格筋線維の損傷および回復・再生機構:筋損傷モデルマウスにおける検討

• Project/Area Number: 18650188
• Research Category: Grant-in-Aid for Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Sports science
• Research Institution: Osaka University
• Principal Investigator: 大平 充宣 Osaka University, 医学系研究科, 教授 (50185378)
• Co-Investigator(Kenkyū-buntansha): 河野 史倫 大阪大学, 医学系研究科, 助教 (90346156)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,200,000 (Direct Cost: ¥3,200,000); Fiscal Year 2007: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
• Keywords: 骨格筋 / 損傷 / 回復 / 再生

Research Abstract

デュシェンヌ型筋ジストロフィー症のモデルであるmdxマウスの骨格筋が損傷と再生を繰り返す機構の解明を目指した。また、その一手段とした炎症反応の影響を追求する実験では、炎症性サイトカインであるインターロイキン6(IL-6)の受容体ブロック(MRI6-1)やマクロファージコロニー刺激因子欠損マウス(op/op)も使用して、筋再生機構の解明に迫った。
筋衛星細胞は筋線維膜下に存在し、筋の発育や負荷の増大に伴う肥大、および筋損傷からの再生時における核の形成に非常に重要な役割を果たす。逆に抗重力筋活動抑制は、衛星細胞数および活性を低下させる。その結果誘発される筋核数の減少に起因してタンパク質合成が抑制されるために、筋萎縮が起こるという示唆もある。そこで我々は、筋の可塑機構における衛星細胞の役割に注目した研究を実施した。さらに、機械的負荷等に対する衛星細胞の反応に、マクロファージやIL-6が如何なる役割を果たすのかも追求した。
その結果、筋の萎縮からの回復には、衛星細胞数の増加が重要な役割を果たしているという示唆が得られたが、op/opマウスではそれが起こらず、萎縮の回復も認められなかった。マクロファージの重要な関与が示唆される。そこで、他のマウスで増やしたマクロファージをop/opマウスに移植する実験に着手した。腱切断および神経切除により機械的負荷および神経活動を除去した場合、mdxマウス骨格筋の壊死からの再生は促進されなかったのみならず、深刻な筋線維萎縮を招いた。また、機械的負荷そのものが、骨格筋におけるタンパク質合成を促進する生理的刺激となっていることも分かった。

Research Products

• [Journal Article] Role(s) of nucleoli, phosphorylation of ribosomal protein S6 and/or HSP27 in the regulation of muscle mass. (2007)
  • Author(s): Kawano, F, Y. Matsuoka, Y. Oke, Y. Higo, M. Terada, X.D. Wang, N. Nakai, H. Fukuda, S. Imajo-Ohmi, and Y. Ohira.
  • Journal Title: Am. J. Physiol. Cell Physiol. 293
  • Peer Reviewed
• [Journal Article] Effects of mechanical and neural stimuli on the properties of soleus muscle fibers in mdx mice. (2007)
  • Author(s): Lan, Y.B., M. Terada, Y. Higo, F. Kawano, Y. Matsuoka, X.D. Wang, N. Nakai, and Y. Ohira.
  • Journal Title: Jpn. J. Aerosp. Environ. Med. 44 Pages: 19-29
  • Peer Reviewed
• [Journal Article] Responses of vastus lateralis muscle fibers to cycling training with different loading parameters in human. (2007)
  • Author(s): Terada, M., E. Lyubaeva, T. Ohira, A. Netreba, F. Kawano, H. Okabe, T. Aoyama, K. Imaizumi, O. Vinogradova, and Y. Ohira.
  • Journal Title: Jpn. J. Aerospace. Environ. Med. 44 Pages: 59-64
  • Peer Reviewed
• [Journal Article] 宇宙環境暴露および老化による骨格筋の萎縮 (2007)
  • Author(s): 後藤勝正、大平充宣
  • Journal Title: 宇宙航空環境医学 44 Pages: 49-58
  • NAID: 10020020499
  • Peer Reviewed
• [Journal Article] Investigation of the mechanism responsible for muscle atrophy and countermeasures in microgravity environment: Role(s)of mechanical load and/or satellite cells. (2007)
  • Author(s): Ohira, Y., X.D. Wang, F. Kawano, M. Terada, Y. Matsuoka, Y. Higo, T. Ohira, A. Kojima, K. Goto, and T. Yoshioka.
  • Journal Title: Proceedings of the 1st International Space Medicine Symposium 2007 in Sapporo Pages: 91-96
  • Peer Reviewed
• [Journal Article] Effects of mechanical and neural stimuli on the properties of soleus muscle fibers in mdx mice.
  • Author(s): Lan, Y.B., M.Terada, Y.Higo, F.Kawano, Y.Matsuoka, X.D.Wang, N.Nakai, Y.Ohira
  • Journal Title: Jpn. J. Aerosp. Environ. Med. (in press)
• [Journal Article] Investigation of the mechanism responsible for muscle atrophy and countermeasures in microgravity environment : Role(s) of mechanical load and/or satellite cells.
  • Author(s): Ohira, Y., X.D.Wang, F.Kawano, M.Terada, Y.Matsuoka, Y.Higo, T.Ohira, A.Kojima, K.Goto, T.Yoshioka
  • Journal Title: Proceedings for the international symposium on space Medicine, Sapporo (in press)
• [Journal Article] Role(s) of nucleoli phosphorylation of ribosomal protein S6 and/or HSP27 in the regulation of muscle mass.
  • Author(s): Kawano F., Y.Matsuoka, Y.Oke, Y.Higo, M.Terada, X.D.Wang, N.Nakai, H.Fukuda, S.Imajoh-Ohmi, Y.Ohira
  • Journal Title: Am. J. Physiol. Cell Physiol. (in press)
• [Presentation] Geranylgeranylaceton increases protein content and heat stress protein 72 expression in skeletal muscle cells. (2007)
  • Author(s): Goto, K., S. Morioka, T. Naito, A. Kojima, T. Akema, H. Fujiya, T. Sugiura, Y. Ohira, and T. Yoshioka.
  • Organizer: 23rd Annual Meet. of Am. Soc. Gravit. Space Biol.
  • Place of Presentation: Moffett Field, Ca., U.S.A.
  • Year and Date: 2007-10-27
• [Presentation] Responses of protein expression to cardiotoxin-induced muscle injury. (2007)
  • Author(s): Kawano, F., M. Terada, N. Nakai, T. Ohira, Y. Higo, N. Nishimoto, and Y. Ohira.
  • Organizer: 23rd Annual Meet. of Am. Soc. Gravit. Space Biol.
  • Place of Presentation: Moffett Field, Ca., U.S.A.
  • Year and Date: 2007-10-27
• [Presentation] Effects of inhibited neural and/or mechanical stimuli on the water content and dry weight in rat hindlimb muscles. (2007)
  • Author(s): Wang, X.D., M. Danda, M. Terada, F. Kawano, T. Ohira, Y. Higo, Y. Nakajima, N. Nakai, K. Goto, and Y. Ohira.
  • Organizer: 23rd Annual Meet. of Am. Soc. Gravit. Space Biol.
  • Place of Presentation: Moffett Field, Ca., U.S.A.
  • Year and Date: 2007-10-27
• [Presentation] Are the responses of adductor longus muscle to gravitational unloading in Wistar Hannover rats region-specific? (2007)
  • Author(s): Ohira, T., X.D. Wang, M. Terada, F. Kawano, Y. Higo, N. Nakai, T. Ochiai, J. Gyotoku, N. Nishimoto, and Y. Ohira
  • Organizer: 23rd Annual Meet. of Am. Soc. Gravit. Space Biol.
  • Place of Presentation: Moffett Field, Ca., U.S.A.
  • Year and Date: 2007-10-26
• [Presentation] Responses of back muscle fibers in Sprague-Dawley rats to spaceflight. (2007)
  • Author(s): Terada, M., F. Kawano, H. Kume, T. Ohira, Y. Higo, Y. Nakajima, X.D. Wang, N. Nakai, W.E. Hinds, and Y. Ohira
  • Organizer: 23rd Annual Meet. of Am. Soc. Gravit. Space Biol.
  • Place of Presentation: Moffett Field, Ca., U.S.A.
  • Year and Date: 2007-10-26
• [Presentation] Responses of body composition and hematological and muscular properties of meriones unguiculatus to gravitational unloading. (2007)
  • Author(s): Nakajima, Y., M. Terada, F. Kawano, H. Sumi, Y. Shimizu, T. Ohira, Y. Higo, X.D. Wang, N. Nakai, and Y. Ohira
  • Organizer: 23rd Annual Meet. of Am. Soc. Gravit. Space Biol.
  • Place of Presentation: Moffett Field, Ca., U.S.A.
  • Year and Date: 2007-10-26
• [Presentation] Peroxisome proliferators-activated receptor α (PPARα) agonist, WY-14,643, increased leucine-induced activation of translation initiation in C2C12 cells. (2007)
  • Author(s): Nakai, N., F. Kawano, M. Terada, and Y. Ohira
  • Organizer: 12th International Congress of World Muscle Society
  • Place of Presentation: Messina, Sicily, Italy
  • Year and Date: 2007-10-19
• [Presentation] The characters of soleus muscle fibers of mdx mice with different distribution of myonuclei. (2007)
  • Author(s): Terada, M., F. Kawano, Y. Higo, T. Ohira, X. Wang, N. Nakai, and Y. Ohira
  • Organizer: 12th International Congress of World Muscle Society
  • Place of Presentation: Messina, Sicily, Italy
  • Year and Date: 2007-10-18