Regulation of osteoclast function by AMPK activity

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592240
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: YORITO Anamizu 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (70302693)
• Co-Investigator(Kenkyū-buntansha): MIYAZAKI Tsuyoshi 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (50376480) ; TANAKA Sakae 東京大学, 医学部附属病院・整形外科, 教授 (50282661)
• Project Period (FY): 2011 – 2013
• Keywords: シグナル伝達 / 破骨細胞

Research Abstract

AMPK is a metabolic master switch that mediates the adaptation of the cell to variations in the nutritional environment. Its activity is stimulated by increases in the intracellular AMP/ATP ratio in response to stresses such as exercise, hypoxia, and glucose deprivation. To test whether modulating AMPK activity would affect osteoclast function, we used adenovirus vectors containing dominant negative (a1DN , a2DN) or constitutively active (a1CA , a2CA) forms of AMPK catalytic subunits (a1 and a2). The phosphorylation level of acetyl-CoA carboxylase at Ser-79, a direct target of AMPK, was modulated by adenovirus-mediated expression of the AMPK mutants. Modulation of AMPK activity did not affect osteoclast survival or bone resorption, indicating that AMPK is not involved in ATP depletion-induced bone resorption.

Research Products

• [Journal Article] Anti-apoptotic Bcl-2 family member Mcl-1 regulates cell viability and bone-resorbing activity of osteoclasts (2014)
  • Author(s): Masuda H,Hirose ],Omata Y,Tokuyama N,Yasui T,Kadono Y,Miyazaki T,Tanaka S
  • Journal Title: Bone Volume: 58 (Epub 2013 Oct 2) Pages: 1-10
  • DOI: 10.1016/j.bone.2013.09.020
• [Journal Article] A review of denosumab for the treatment of osteoporosis (2014)
  • Author(s): Miyazaki T,Tokimura F,Tanaka S
  • Journal Title: Patient Prefer Adherence Volume: 8 Pages: 463-471
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• [Journal Article] Two novel sandwich ELISAs identify PAD4 levels and PAD4 autoantibodies in patients with rheumatoid arthritis (2013)
  • Author(s): Ishigami A,Uchida Y,Miyazaki T,Handa S,Choi EK,Kim YS,Kasahara Y,Maruyama N
  • Journal Title: Mod Rheumatol Volume: 23 Pages: 794-803
  • DOI: 10.1007/s10165-0120-0748-0
• [Journal Article] Intracellular and extracellular ATP coordinately regulate the inverse correlation between osteoclast survival and bone resorption (2012)
  • Author(s): Miyazaki T,Iwasawa M,Nakashima T,Mori S,Shigemoto K,Nakamura H,Katagiri H,Takayanagi H,Tanaka S
  • Journal Title: J Biol Chem Volume: 287(45) Pages: 37808-23
  • DOI: 10.1074/jbc.M112.385369
• [Journal Article] 3,4-Diaminopyridine improves neuromuscular transmission in a MuSK antibody-induced mouse model of myasthenia gravis (2012)
  • Author(s): Mori S,Kishi M,Kubo S,Akiyoshi T,Yamada S,Miyazaki T,Konishi T,Maruyama N,Shigemoto K
  • Journal Title: J Neuroimmunol Volume: 245 Pages: 75-8
  • DOI: 10.1016/j.jneuroim.2012.02.010
• [Journal Article] Antibodies against muscle-specific kinase impair both presynaptic and postsynaptic functions in a murine model of myasthenia gravis (2012)
  • Author(s): Mori S,Kubo S,Akiyoshi T,Yamada S,Miyazaki T,Hotta H,Desaki J,Kishi M,Konishi T,Nishino Y,Miyazawa A,Maruyama N,Shigemoto K
  • Journal Title: Am J Pathol Volume: 180 (ISSN:0002-9440) Pages: 798-810
  • DOI: 10.1016/j.ajpath.2011.10.031
• [Journal Article] Cytoplasmic Superoxide Causes Bone Fragility Owing to Low-Turnover Osteoporosis and Impaired CollagenCross-Linking (2011)
  • Author(s): Nojiri H,Saita Y,Morikawa D,Kobayashi K,Tsuda C,Miyazaki T,Saito M,Marumo M,Yonezawa I,Kaneko K,ShirasawaT,and Shimizu T
  • Journal Title: J Bone Miner Res Volume: 26 Pages: 2682-94
  • DOI: 10.1002/jbmr.489
• [Presentation] Muscle fiber type specific pathology in aging mouse (2012)
  • Author(s): Fukunaga,T.,Kubo,S.,Mori,S.,Miyazaki,T.,Higami,Y. and Shigemoto,K.
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] 老齢マウスの筋繊維タイプ特異的な筋萎縮の病態解明 (2012)
  • Author(s): 福永大地、森秀一、久保幸穂、中山亮、村瀬尚哉、宮崎剛、樋上賀一、重本和宏
  • Organizer: 第32回日本基礎老化学会大会
  • Place of Presentation: 千葉県船橋
  • Year and Date: 20120726-27
• [Presentation] A novel murine model of myasthenia gravis with MuSK antibodies (2012)
  • Author(s): Mori,S.,Kubo,S.,Akiyoshi,T.,Yamada,S.,Miyazaki,T.,Hotta,H.,Desaki,J.,Kishi,M.,Konishi,T.,Maruyama,N. and Shigemoto,K.
  • Organizer: 12th International conference on myasthenia gravis and related disorders
  • Place of Presentation: New York
  • Year and Date: 20120521-23
• [Presentation] Examination of the treatment of myasthenia gravis with anti-MuSK antibodies using an experimental autoimmune animal model (2012)
  • Author(s): Mori,S.,Kubo,S.,Akiyoshi,T.,Yamada,S.,Miyazaki,T.,Hotta,H.,Desaki,J.,Kishi,M.,Konishi,T.,Maruyama,N. and Shigemoto,K.
  • Organizer: 12th International conference on myasthenia gravis and related disorders
  • Place of Presentation: New York
  • Year and Date: 20120521-23
• [Presentation] Maintenance of mitochondrial DNA copy number is essential for osteoclast survival and bone resorption (2011)
  • Author(s): Miyazaki T,Mori S,Shigemoto K,Larsson N,Nakamura T,Kato S,Nakashima T,Takayanagi H,Tanaka S
  • Organizer: 1^<st> Bio-Rheumatology International Congress Tokyo 8^<th> GARN meeting
  • Place of Presentation: Tokyo. Maihama
  • Year and Date: 20111114-16
• [Presentation] 破骨細胞特異的ノックアウトマウスによる抗アポトーシス分子Bcl-xLの機能解析ーBcl-xLは破骨細胞の骨吸収に抑制的に働く- (2011)
  • Author(s): 岩津三康、永瀬雄一、宮崎剛、中村耕三、田中栄
  • Organizer: 第84回日本整形外科学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20110512-15