Functional and morphological analysis of mitochondria in osteoclastic bone resorption

• 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
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 骨関節破壊 / 破骨細胞 / ミトコンドリア / 骨吸収 / 関節リウマチ

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) Issue: 7 Pages: 712-8
  • 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 (2012)
  • Author(s): Muraki S, Akune T, Oka H, Ishimoto Y, Nagata K, Yoshida M, Tokimura F, Nakamura K, Kawaguchi H, Yoshimura N
  • Journal Title: A longitudinal cohort study. Osteoporosis Int (inpress) Volume: 21(Epub ahead of print) Issue: 2 Pages: 459-466
  • 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) Issue: 5 Pages: 1147-56
  • 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) Issue: 45 Pages: 34808-23
  • 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.)
  • NAID: 10031189176
  • 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. , Kishi, M., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Konishi, T., Maruyama, N., and Shigemoto, K.
  • Journal Title: Journal of neuroimmunology Volume: 245 Issue: 1-2 Pages: 75-78
  • 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, et al
  • Journal Title: J Orthop Sci Volume: 16 Issue: 6 Pages: 768-777
  • 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) Issue: 12 Pages: 3486-94
  • 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 (2011)
  • Author(s): Muraki S, et al
  • Journal Title: Arthritis Rheum-US Volume: 63 Issue: 12 Pages: 3859-3864
  • 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 ROAD study (2011)
  • Author(s): Muraki S, et al
  • Journal Title: Spine Volume: 36 Issue: 16 Pages: 1312-1319
  • DOI: 10.1097/brs.0b013e3181fa60d1
  • Peer Reviewed
• [Journal Article] Owing to Low-Turnover Osteoporosis and Impaired CollagenCross-Linking (2011)
  • Author(s): Hidetoshi Nojiri, Yoshitomo Saita, Daichi Morikawa, Keiji Kobayashi, Chizuru Tsuda, Tsuyoshi Miyazaki, Mitsuru Saito, Keishi Marumo, Ikuho Yonezawa, Kazuo Kaneko, Takuji Shirasawa, and Takahiko Shimizu
  • Journal Title: J Bone Miner Res Volume: 26(11) Issue: 11 Pages: 2682-94
  • 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) Issue: 9 Pages: 1227-34
  • 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) Issue: 5 Pages: 444-51
  • DOI: 10.1007/s10165-010-0307-5
  • NAID: 10027646934
  • 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) Issue: 4 Pages: 446-50
  • DOI: 10.1007/s00774-009-0147-6
  • Peer Reviewed
• [Journal Article] Neutrophil CD64 expression as a diagnostic marker for local infection and crystal-induced arthritis (2010)
  • Author(s): Toru Doi, Tsuyoshi Miyazaki, Jinju Nishino, Sakae Tanaka, Toshihiro Matsui, Akiko Komiya, Seizo Yamamoto, Fumiaki Tokimura, Toshihito Mori, Keita Nishimura, Narutaka Katoh, Jun Hasegawa, Yasunori Omata, Takashi Matsushita, Shigeto Tohma
  • Journal Title: Mod Rheumatol Volume: 20(6) Issue: 6 Pages: 573-9
  • DOI: 10.1007/s10165-010-0322-6
  • NAID: 10027647433
  • 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 Issue: 2 Pages: 100-107
  • DOI: 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
  • NAID: 10027273521
  • 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, Akune T, Oka H, En-yo Y, Yoshida M, Saika A, Suzuki T, Yoshida H, Ishibashi H, Tokimura F, Yamamoto S, Nakamura K, Kawaguchi H, Yoshimura N.
  • Journal Title: Osteoarthritis Cartilage Volume: 18 Pages: 1227-1234
  • 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, Akune T, Oka H, En-Yo Y, Yoshida M, Saika A, Suzuki T, Yoshida H, Ishibashi H, Tokimura F, Yamamoto S, Nakamura K, Kawaguchi H, Yoshimura N.
  • Journal Title: Mod Rheumatof Volume: 20 Pages: 444-451
  • NAID: 10027646934
  • 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, Fuku N, Chiba Y, Tokimura F, Hosoi T, Kimbara Y, Tamura Y, Araki A, Tanaka M, Ito H.
  • Journal Title: J Bone Miner Metab. Volume: 28 Pages: 446-450
  • Peer Reviewed
• [Journal Article] Neutrophil CD64 expression as a diagnostic marker for local infection and crystal-induced arthritis (2010)
  • Author(s): Toru Doi, Tsuyoshi Miyazaki, Jinju Nishino, Sakae Tanaka, Toshihiro Matsui, Akiko Komiya, Seizo Yamamoto, Fumiaki Tokimura, Toshihito Mori, Keita Nishimura, Narutaka Katoh, Jun Hasegawa, Yasunori Omata, Takashi Matsushita, Shigeto Tohma
  • Journal Title: Mod Rheumatol Volume: 20 Pages: 473-579
  • NAID: 10027647433
  • Peer Reviewed
• [Journal Article] 腿神経ブロックが人工膝関節全置換術後の膝伸展筋力に与える影響 (2010)
  • Author(s): 山神良太、宮本恵成、濱路博、穴水依人、時村文秋
  • Journal Title: 日本関節鏡・膝・スポーツ整形外科学会雑誌 Volume: 36 Pages: 112-113
• [Journal Article] Regulation of apoptosis and activity of the osteoclast (2010)
  • Author(s): Tsuyoshi Miyazaki, Sakae Tanaka
  • Journal Title: Immun., Endoc.& Metab.Agents in Med.Chem. Volume: 10 Pages: 100-107
  • 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
• [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
• [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
• [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: 9th Japanese-French Symposium for ‘muscular dystrophy’
  • Place of Presentation: 東京
• [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] 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
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Maintenance of mitochondrial DNA copy number is essential for osteoclast survival and bone resorption (2011)
  • Author(s): Tsuyoshi Miyazaki, Shuuichi Mori, Kazuhiro Shigemoto, Nils-Goran Larsson, Takeshi Nakamura, Shigekaki Kato, Tomoki Nakashima, Hiroshi Takayanagi, Sakae Tanaka
  • Organizer: 1^<st> Bio-Rheumatology Internationla Congress Tokyo 8^<th> GARN meeting Tokyo
  • Place of Presentation: Maihama, Japan
• [Presentation] 腿神経ブロックが人工膝関節全置換術後の膝伸展筋力に与える影響 (2010)
  • Author(s): 山神良太、宮本恵成、濱路博、穴水依人、時村文秋
  • Organizer: 第2回日本関節鏡・膝・スポーツ整形外科学会
  • Place of Presentation: 沖縄
  • Year and Date: 2010-07-03
• [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
• [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
• [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
• [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
• [Presentation] ntracellular superoxide dismutase deficiency decreased bone mass in vivo by impairment of cell viability and redox balance in osteoblasts. (2010)
  • Author(s): Yoshitomo Saita, Hidetoshi Nojiri, Chizuru Tsuda, Tsuyoshi Miyazaki, Daichi Morikawa, Kazuo Kaneko, Takahiko Shimizu
  • Organizer: Thirty-second Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Toronto, Canada
• [Book] FLEX (2011)
  • Author(s): 宮本恵成、壁遡
  • Publisher: カレントテラピー
• [Book] 骨・関節と加齢 (2010)
  • Author(s): 宮崎剛、田中栄
  • Publisher: ANTI-AGING MEDICEIN
• [Book] 神経筋接合部の異常と筋萎縮 (2010)
  • Author(s): 重本和宏、森秀一、久保幸穂、山田茂、秋好沢諭、宮崎剛
  • Publisher: 老年医学update2010-11