Molecular Analysis of Initiation and Termination in Bone Formation

• Project/Area Number: 19390399
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Keio University
• Principal Investigator: MATSUO Koichi Keio University, 医学部, 准教授 (40229422)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI Toru 慶應義塾大学, 医学部, 助教 (50338092) ; TAKADA Yasunari 慶應義塾大学, 医学部, 助教 (40407086) ; TOYAMA Yoshiaki 慶應義塾大学, 医学部, 教授 (40129549)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2008: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000); Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: 骨・軟骨代謝 / 骨リモデリング / 骨硬化症 / Fral / トランスジェニックマウス / 骨芽細胞 / 破骨細胞 / カップリング / 耳小骨

Research Abstract

本研究では、発生過程と骨折治癒過程における内軟骨性骨化の起動メカニズムを解明した。発生過程の軟骨形成は正常で、骨折時の炎症性メディエーターの産生が低下しているトランスジェニックマウスを解析したところ、骨折線の融合不全を起こしていた。徐放性のPGE2ペレットを骨折線近傍に投与したところ、軟骨形成が回復し、骨折融合が促進された。すなわち、骨形成プログラムの起動メカニズムが発生過程と修復過程とで異なることが明らかになった。

Research Products

• [Journal Article] Cross-talk among bone cells (2009)
  • Author(s): Matsuo, K.
  • Journal Title: Curr Opin Nephrol Hypertens 0.1097/MNH.0b013e32832b75f1(in press)
• [Journal Article] Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis (2009)
  • Author(s): Irie N, Takada Y, Watanabe Y, Matsuzaki Y, Naruse C, Asano M, Iwakura Y, Suda T, Matsuo K.
  • Journal Title: J. Biol. Chem.(Published on line)
  • Peer Reviewed
• [Journal Article] Bisphosphonate therapy ameliorates hearing loss in mice lacking osteoprotegerin (2009)
  • Author(s): Kanzaki S, Takada Y, Ogawa K, Matsuo K.
  • Journal Title: J. Bone Miner. Res. 24 Pages: 43-49
  • Peer Reviewed
• [Journal Article] Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis. (2009)
  • Author(s): Irie, N., Takada, Y., Watanabe, Y., Matsuzaki, Y., Naruse, C., Asano, M., Iwakura, Y. Suda, T., Matsuo, K.
  • Journal Title: Journal of Biological Chemistry (未定)(印刷中)
  • Peer Reviewed
• [Journal Article] Bisphosphonate therapy ameliorates hearing loss in mice lacking osteo protegerin. (2009)
  • Author(s): Kanzaki, S., Takada, Y., Ogawa, K., Matsuo. K.
  • Journal Title: Journal of Bone and Mineral Research 24 Pages: 43-49
  • Peer Reviewed
• [Journal Article] Cross-talk among bone cells. (2009)
  • Author(s): Matsuo, K.
  • Journal Title: Curr Opin Nephrol Hypertens (未定)(印刷中)
• [Journal Article] Signaling flux redistribution at Toll-like receptor pathway junctions (2008)
  • Author(s): Selvarajoo K, Takada Y, Gohda J, Helmy M, Akira S, Tomita M, Tsuchiya M, Inoue J, Matsuo K.
  • Journal Title: PLoS ONE 3 Pages: 3430-3430
  • Peer Reviewed
• [Journal Article] RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator (2008)
  • Author(s): Hikosaka Y, Nitta T, Ohigashi I, Yano K, Ishimaru N, Hayashi Y, Matsumoto M, Matsuo K, Penninger JM, Takayanagi H, Yokota Y, Yamada H, Yoshikai Y, Inoue J, Akiyama T, Takahama Y.
  • Journal Title: Immunity 29 Pages: 438-450
  • Peer Reviewed
• [Journal Article] Osteoblasts induce Ca^<2+> oscillation-independent NFATc1 activation during osteoclastogenesis (2008)
  • Author(s): Kuroda Y, Hisatsune C, Inoue T, Nakamura T, Matsuo K, Mikoshiba K.
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 8643-8648
  • Peer Reviewed
• [Journal Article] Osteoblasts induce Ca^<2+> oscillation-independent NFATcl activation during osteoclastogenesis. (2008)
  • Author(s): Kuroda, Y, et. al.
  • Journal Title: Proc.Natl.Acad.Sci.USA (印刷中)(未定)
  • Peer Reviewed
• [Journal Article] Osteoclast-osteoblast communication. (2008)
  • Author(s): Matsuo, K. and Irie, N.
  • Journal Title: Arch.Biochem.Biophys. (印刷中)(未定)
  • Peer Reviewed
• [Journal Article] NF-_KB p50 and p52 regulate receptor activator of NF-_KB ligand(RANKL)and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATcl. (2007)
  • Author(s): Yamashita, T, et. al.
  • Journal Title: J.Biol.Chem 282 Pages: 18245-18253
  • Peer Reviewed
• [Presentation] EphB/ephrin-B interactions assist in MSC niche maintenance and contribute to bone remodelling following injury (2009)
  • Author(s): Arthur, A., Stylianou, C., Koblar, S. A., Matsuo, K., Gronthos, S.
  • Organizer: 2nd Joint Meeting of the International Bone & Mineral Society and the Australian and New Zealand Bone & Mineral Society
  • Place of Presentation: Sydney, Austria
• [Presentation] Late expression of c-Fos during osteoclast differentiation determines osteoclast survival and bone mass (2009)
  • Author(s): Takada, Y., Irie, N., Grech, L., Nakamura, T., Kato, S., Wagner, E. F., Matsuo, K.
  • Organizer: 2nd Joint Meeting of the International Bone & Mineral Society and the Australian and New Zealand Bone & Mineral Society
  • Place of Presentation: Sydney, Austria
• [Presentation] Bi-directional signaling between osteoblast and osteoclast, Ephrins, as un-coupling mechanism (2008)
  • Author(s): Matsuo, K.
  • Organizer: Korean Society of Osteoporosis Annual Meeting, Continuing Medical Education, and International Symposium
  • Place of Presentation: Korea(招待講演)
  • Year and Date: 2008-11-16
• [Presentation] Osteoclast-osteoblast interaction (2008)
  • Author(s): Matsuo, K.
  • Organizer: entre hospitalier de l' Universite de Montreal, Hopital Notre-Dame(host, Dr. Johanne Martel-Pelletier)
  • Place of Presentation: Montreal, Canada(招待講演)
  • Year and Date: 2008-09-12
• [Presentation] Bisphosphonate therapy ameliorates bone resorption and hearing loss in mice lacking osteoprotegerin (2008)
  • Author(s): Kanzaki, S., Takada, Y., Ogawa, K., Matsuo, K.
  • Organizer: 8th International Conference on Cholesteatoma & Ear Surgery
  • Place of Presentation: Antalya, Turkey
  • Year and Date: 2008-06-15
• [Presentation] Regulation of osteoblasts by osteoclasts (2008)
  • Author(s): Matsuo, K.
  • Organizer: Forefront on Advanced Bone and Joint Science
  • Place of Presentation: Tokyo, Japan(招待講演)
• [Presentation] Ephrins in osteoclast-osteoblast communication (2008)
  • Author(s): Matsuo, K.
  • Organizer: 30th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Montreal, Canada(招待講演)
• [Presentation] Fra1 and "danger signals" in lung injury and bone fracture (2008)
  • Author(s): Matsuo, K.
  • Organizer: 2nd International Conference on Osteoimmunology
  • Place of Presentation: Rhodos, Greece(招待講演)
• [Presentation] Osteoclast-osteoblast bidirectional signaling (2008)
  • Author(s): Matsuo, K.
  • Organizer: 35th European Symposium on Calcified Tissues
  • Place of Presentation: Barcelona, Spain(招待講演)
• [Presentation] Ephrin signaling in osteoclast-osteoblast cross-talk (2008)
  • Author(s): Matsuo, K.
  • Organizer: IBMS Davos Workshops : Bone Biology & Therapeutics
  • Place of Presentation: Davos, Switzerland(招待講演)
• [Presentation] ephrinA2-EphA2両方向性シグナルによる骨リモデリング開始期の制御 (2008)
  • Author(s): 入江奈緒子, 高田康成, 松尾光
  • Organizer: 第26回日本骨代謝学会
  • Place of Presentation: 大阪
• [Presentation] Ephrin signaling in osteoclast-osteoblast cross-talk (2008)
  • Author(s): Matsuo, K.
  • Organizer: Davos Workshops:Bone Biology & Therapeutics
  • Place of Presentation: Davos,Switzerland
• [Presentation] Regulation of bone remodeling through ephrine-Eph interactions (2007)
  • Author(s): Matsuo, K.
  • Organizer: Seminar at St. Vincent's Institute
  • Place of Presentation: Melbourne, Australia(招待講演)
  • Year and Date: 2007-11-22
• [Presentation] Regulation of bone remodeling through ephrine-Eph interactions (2007)
  • Author(s): Matsuo, K.
  • Organizer: Seminar at St.Vince's Institute
  • Place of Presentation: Melbourne,Australia
  • Year and Date: 2007-11-22
• [Presentation] Ephrins in osteoclast-osteoblast communication (2007)
  • Author(s): Matsuo, K.
  • Organizer: Molecular Signalling in Bone Remodelling : Therapeutic Opportunities
  • Place of Presentation: Sydney, Australia(招待講演)
• [Presentation] Ephrin function in bone cell interaction (2007)
  • Author(s): Matsuo, K.
  • Organizer: "Stem Cell Regulation and Biosciences" The International Symposium/Workshop on Advanced Bone and Joint Science (ABJS)
  • Place of Presentation: Tokyo(招待講演)
• [Presentation] The POZ-Zn Transcriptional Regulator OCZF/LRF Is Induced by RANKL and Increases c-Fos Expression in Osteoclastogenesis (2007)
  • Author(s): Kukita, A., Shobuike, T., Asagiri, M., Takayanagi, H., Pessler, F., Matsuo, K., Kukita, T.
  • Organizer: 29th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Hawaii, USA
• [Presentation] Bidirectional signalling between osteoclasts and osteoblasts as an explanation for coupling : the role of ephrin-Eph (2007)
  • Author(s): Matsuo, K.
  • Organizer: 17th Meeting of the International Bone and Mineral Society (IBMS)
  • Place of Presentation: Montreal, Canada(招待講演)
• [Presentation] Regulation of bone remodeling through cell-cell interaction (2007)
  • Author(s): Matsuo, K.
  • Organizer: Korean Endocrine Society Meeting
  • Place of Presentation: Soul, Korea(招待講演)
• [Presentation] Regulation of bone remodeling through cell-cell interaction. (2007)
  • Author(s): Matsuo, K.
  • Organizer: Korean Endocrine Society Meeting
  • Place of Presentation: Soul.Korea
• [Presentation] Bidirectional signalling between osteoclasts and osteoblasts as an explanation for coupling:the role of ephrin-Eph (2007)
  • Author(s): Matsuo, K.
  • Organizer: 17^<th> Meeting of the International Bone and Mineral Society
  • Place of Presentation: Montreal,Canada
• [Presentation] The POZ-Zn Transcriptional Regulator OCZF/LRF Is Induced by RANKL and Increases c-Fos Expression in Osteoclastogenesis. (2007)
  • Author(s): Kukita, A., Shobuike, T., Asagiri, M., Takayanagi, H., Pessler, F., Matsuo, K., Kukita, T.
  • Organizer: 29^<th> Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Hawaii,USA
• [Presentation] Ephrin function in bone cell interaction."Stem Cell Regulation and Bio sciences" (2007)
  • Author(s): Matsuo, K.
  • Organizer: The International Symposium/Workshop on Advanced Bone and Joint Science (ABJS)
  • Place of Presentation: Tokyo
• [Presentation] Ephrins in osteoclast-osteoblast communication. (2007)
  • Author(s): Matsuo, K.
  • Organizer: Molecular Signalling in Bone Remodelling:Therapeutic Opportunities
  • Place of Presentation: Sydney,Australia
• [Book] 目で見る Bone Biology : 骨芽細胞と破骨細胞のクロストーク : エフリンとエフ(8(3)) (2009)
  • Author(s): 松尾光一、入江奈緒子
  • Publisher: 骨粗鬆症治療(印刷中)
• [Book] 骨芽細胞と破骨細胞の細胞間クロストーク(27(6)) (2009)
  • Author(s): 松尾光一
  • Publisher: 実験医学
• [Book] 骨生物学の新機軸-Osteonetwork とOsteocrine System-(63(11)) (2008)
  • Author(s): 山口朗、松尾光一、今村健志、田中栄、福本誠二
  • Publisher: 最新医学
• [Book] 破骨細胞・骨芽細胞における細胞間相互作用の分子メカニズム(27(3)) (2008)
  • Author(s): 松尾光一
  • Publisher: 内分泌・糖尿病科
• [Book] 骨リモデリングと骨質(18(3)) (2008)
  • Author(s): 佐野元市郎、 松尾光一
  • Publisher: Clin. Calcium
• [Book] AP-1による骨免疫制御(21(1)) (2008)
  • Author(s): 松尾光一
  • Publisher: 腎と骨代謝
• [Book] AP-1の骨と免疫系における機能(20(8)) (2007)
  • Author(s): 松尾光一、高田康成
  • Publisher: 骨・関節・靱帯
• [Book] 骨免疫学は偶然か必然か(20(8)) (2007)
  • Author(s): 松尾光一
  • Publisher: 骨・関節・靱帯
• [Book] エフリンとエフによる骨代謝調節(21(6)) (2007)
  • Author(s): 松尾光一
  • Publisher: THE BONE
• [Remarks]
  • URL: http://www.matsuo-lab.com