Functional and morphological analysis of mitochondria in osteoclastic bone resorption

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591698
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: TOKIMURA Fumiaki 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 (80242147)
• 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)
• Co-Investigator(Renkei-kenkyūsha): TANAKA Sakae 東京大学, 医学部附属病院・整形外科, 教授 (50282661)
• Project Period (FY): 2010 – 2012
• Keywords: 骨関節破壊 / 破骨細胞

Research Abstract

To explore the relationship between osteoclastic bone resorption and mitochondrial morphology, we constructed adenoviruses carrying wild type Drp1 or dominant negative form of Drp1 (Drp1K38A, a point mutation at Lys-38 to Ala). Infection of AxDrp1K38A did not have any effect on osteoclast survival. However, the expression of Drp1K38A caused cytoskeletal disorganization of osteoclasts and suppressed pit-forming activity of the cells in vitro. These results suggest a potential application of mitochondrial fission to control osteoclastic bone resorption.

Research Products

• [Journal Article] Incidence and risk factors for radiographic lumbar spondylosis and lower back pain in Japanese men and women: the ROAD study. (2012)
  • Author(s): Muraki S, Tokimura F
  • Journal Title: Osteoarthritis Cartilage. Volume: 20(7) Pages: 712-8
  • DOI: doi:10.1016/j.joca.2012.03.009
  • Peer Reviewed
• [Journal Article] Physical performance, bone and joint diseases, and incidence of falls in Japanese men and women: a longitudinal cohort study. (2012)
  • Author(s): Muraki S, Tokimura F
  • Journal Title: Osteoporos Int. Volume: 21(Epub ahead of print)
  • DOI: doi:10.1007/s00198-012-1967-0
  • Peer Reviewed
• [Journal Article] Incidence and risk factors for radiographic knee osteoarthritis and knee pain in Japanese men and women: a longitudinal population-based cohort study. (2012)
  • Author(s): Muraki S, Tokimura F
  • Journal Title: Arthritis Rheum. Volume: 64(5) Pages: 1147-56
  • DOI: doi:10.1002/art.33508
  • Peer Reviewed
• [Journal Article] Intracellular and extracellular ATP coordinately regulate the inverse correlation between osteoclast survival and bone resorption. (2012)
  • Author(s): Miyazaki T, Iwasawa M
  • Journal Title: J Biol Chem. Volume: 287(45) Pages: 34808-23
  • DOI: doi:10.1074/jbc.M112.385369
  • Peer Reviewed
• [Journal Article] Two novel sandwich ELISAs identify PAD4 levels and PAD4 autoantibodies in patients with rheumatoid arthritis. (2012)
  • Author(s): Ishigami A, Miyazaki T
  • Journal Title: Mod Rheumatol. Volume: (Epub ahead of print.)
  • Peer Reviewed
• [Journal Article] 3,4-Diaminopyridine improves neuromuscular transmission in a MuSK antibody-induced mouse model of myasthenia gravis. (2012)
  • Author(s): Mori S, Miyazaki T
  • Journal Title: J Neuroimmunol. Volume: 245 Pages: 75-8
  • DOI: DOI:10.1016/j.jneuroim.2012.02.010
  • Peer Reviewed
• [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, Miyazaki T
  • Journal Title: Am J Pathol. Volume: 180 Pages: 798-810
  • DOI: DOI:10.1016/j.jneuroim.2012.02.010
  • Peer Reviewed
• [Journal Article] Reference values for hand grip strength, muscle mass, walking time, and one-leg standing time as indices for locomotive syndrome and associated disability : the second survey of the ROAD study. (2011)
  • Author(s): Yoshimura N, Tokimura F
  • Journal Title: J Orthop Sci. Volume: 16(6) Pages: 768-77
  • DOI: doi:10.1007/s00776-011-0160-1
  • Peer Reviewed
• [Journal Article] Are bone and serum cefazolin concentrations adequate for antimicrobial prophylaxis? (2011)
  • Author(s): Yamada K, Tokimura F
  • Journal Title: Clin Orthop Relat Res. Volume: 469(12) Pages: 3486-94
  • DOI: doi:10.1007/s11999-011-2111-8
  • Peer Reviewed
• [Journal Article] Independent association of joint space narrowing and osteophyte formation at the knee with health-related quality of life in Japan : across-sectional study. (2011)
  • Author(s): Muraki S, Tokimura F
  • Journal Title: Arthritis Rheum. Volume: 63(12) Pages: 3859-64
  • DOI: doi:10.1002/art.30641
  • Peer Reviewed
• [Journal Article] Health-related quality of life in subjects with low back pain and knee pain in a population-based cohort study of Japanese men : the Research on Osteoarthritis Against Disability study. (2011)
  • Author(s): Muraki S, Tokimura F
  • Journal Title: Spine Volume: 36(16) Pages: 1312-9
  • DOI: doi:10.1097/BRS.0b013e3181fa60d1
  • Peer Reviewed
• [Journal Article] Cytoplasmic Superoxide Causes Bone Fragility Owing to Low-Turnover Osteoporosis and Impaired Collagen Cross-Linking. (2011)
  • Author(s): Nojiri H, Miyazaki T
  • Journal Title: J Bone Miner Res Volume: 26 Pages: 2682-94
  • DOI: DOI:10.1002/jbmr.489
  • Peer Reviewed
• [Journal Article] Association of radiographic and symptomatic knee osteoarthritis with health-related quality of life in a population-based cohort study in Japan : the ROAD study. (2010)
  • Author(s): Muraki S, Tokimura F
  • Journal Title: Osteoarthritis Cartilage. Volume: 18(9) Pages: 1227-34
  • DOI: doi:10.1016/j.joca.2010.06.001
  • Peer Reviewed
• [Journal Article] Impact of knee and low back pain on health-related quality of life in Japanese women : the Research on Osteoarthritis Against Disability (ROAD). (2010)
  • Author(s): Muraki S, Tokimura F
  • Journal Title: Mod Rheumatol. Volume: 20(5) Pages: 444-51
  • DOI: doi:10.1007/s10165-010-0307-5
  • Peer Reviewed
• [Journal Article] Cooperative effect of serum 25-hydroxyvitamin D concentration and a polymorphism of transforming growth factor-beta1 gene on the prevalence of vertebral fractures in postmenopausal osteoporosis. (2010)
  • Author(s): Mori S, Tokimura F
  • Journal Title: J Bone Miner Metab. Volume: 28(4) Pages: 446-50
  • DOI: doi:10.1007/s00774-009-0147-6
  • Peer Reviewed
• [Journal Article] Neutrophil CD64 expression as a diagnostic marker for local infection and crystal-induced arthritis1 (2010)
  • Author(s): Doi T, Miyazaki T
  • Journal Title: Mod Rheumatol Volume: 20(6) Pages: 573-9
  • DOI: doi:10.1007/s10165-010-0322-6
  • Peer Reviewed
• [Journal Article] Regulation of apoptosis and activity of the osteoclast. Immun., Endoc. & Metab. (2010)
  • Author(s): Miyazaki T and Tanaka S
  • Journal Title: Agents in Med. Chem. Volume: 10 Pages: 100-107
  • DOI: DOI:http://dx.doi.org/10.2174/187152210793176974
  • Peer Reviewed
• [Journal Article] Muscle weakness and neuromuscular junctions in aging and disease. (2010)
  • Author(s): Shigemoto K, Miyazaki T.
  • Journal Title: Geriatr Gerontol Int Volume: 10 Pages: 137-147
  • DOI: DOI:10.1111/j.1447-0594.2010.00608
  • Peer Reviewed
• [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] Maintenance of mitochondrial DNA copy number is essential for osteoclast survival and bone resorption. (2011)
  • Author(s): MiyazakiT, Mori S, Shigemoto K, Larsson N, Nakamura T, Kato S, Nakashima T, Takayanagi H, Tanaka S
  • Organizer: 1^<st> Bio-Rheumatology Internationla Congress Tokyo 8^<th> GARN meeting Tokyo.
  • Place of Presentation: Maihama
  • Year and Date: 20111114-16
• [Presentation] Distinct mechanisms between divalent and monovalent MuSK antibodies involved with dysfunction of MuSK leading to myasthenia gravis. (2011)
  • Author(s): Mori S, Kubo S, Yamada S, Miyazaki T, Shigemoto K.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington, D.C. USA
  • Year and Date: 20111113-18
• [Presentation] スーパーオキサイドディスムターゼ1(SOD1)欠損は低代謝回転型骨量減少と加齢性コラーゲン架橋変化を引き起こし骨脆弱化する (2011)
  • Author(s): 野尻英俊、斎田良知、森川大智、小林慶司、宮崎剛、斎藤充、丸毛啓史、金子和夫、清水孝彦
  • Organizer: 第29回日本骨代謝学会学術集会
  • Place of Presentation: 前橋
  • Year and Date: 20111019-21
• [Presentation] スーパーオキサイドディスムターゼ1(SOD1)による骨代謝制御機構の解析 (2011)
  • Author(s): 斎田良知、野尻英俊、森川大智、宮崎剛、麻生義則、金子和夫、清水孝彦
  • Organizer: 第26回日本整形外科学会基礎学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20110728-30
• [Presentation] 抗MuSK抗体による重症筋無力症の動物モデル作製と病態機序の解明 (2011)
  • Author(s): 重本和宏、森秀一、山田茂、久保幸穂、宮崎剛、秋好沢論、岸雅彦、小西哲郎
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 20110518-20
• [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-Bcl-xLは破骨細胞の骨吸収に抑制的に働く- (2011)
  • Author(s): 岩澤三康、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
• [Presentation] 細胞質酸化ストレスの増加は骨量および骨質の低下を引き起こす (2011)
  • Author(s): 森川大智、野尻英俊、斎田良和、小林慶司、宮崎剛、齋藤充、丸毛啓史、金子和夫、清水孝彦
  • 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
• [Presentation] Distinct mechanisms between divalent and monovalent MuSK antibodies involved with dysfunction of MuSK leading to myasthenia gravis. (2011)
  • Author(s): Mori S, Kubo S, Yamada S, Miyazaki T, Shigemoto K.
  • Organizer: 第34回日本神経科学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-15
• [Presentation] Intracellular superoxide dismutase deficiency decreased bone mass in vivo by impairment of cell viability and redox balance in osteoblasts.Thirty-second (2010)
  • Author(s): Saita Y, Nojiri H, Tsuda C, Miyazaki T, Morikawa D, Kaneko K, Shimizu T
  • Organizer: Annual Meeting of the American Society for Bone and Mineral Research.
  • Place of Presentation: Toronto, Canada
  • Year and Date: 20101015-19
• [Presentation] 筋は逆行性シグナルにより筋・運動神経を維持する (2010)
  • Author(s): 森秀一、久保幸穂、秋好沢論、山田茂、宮崎剛、重本和宏
  • Organizer: 日本基礎老化学会大33回大会
  • Place of Presentation: 名古屋
  • Year and Date: 20100617-18
• [Presentation] Mouse lacking in intracellular superoxide dismutase increased reactive oxygen spices in osteoblasts and suppressed osteoblastic ability leading to osteoporotic phenotypes in bone. (2010)
  • Author(s): SaitaY, Nojiri H, Tsuda C, Miyazaki T, Morikawa D, Kaneko K, Shimizu T
  • Organizer: IOF World Congress on Osteoporosis & 10th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis
  • Place of Presentation: Italy
  • Year and Date: 20100505-08
• [Presentation] Bcl-xL regulates osteoclastic bone resorption via extracellular matrix component protein. (2010)
  • Author(s): 宮崎剛
  • Organizer: 第4回Bone Research Seminar
  • Place of Presentation: 東京
  • Year and Date: 20100219-20