Bone formation system in medaka

• Project/Area Number: 23370090
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: KUDO Akira 東京工業大学, 生命理工学研究科, 教授 (70178002)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥20,020,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥4,620,000); Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: メダカ / 骨形成 / 骨芽細胞 / 破骨細胞 / 骨リモデリング / 骨折修復 / 咽頭歯骨 / eda / 咽頭歯 / 骨折 / TGFbeta / ぺリオスチン / 椎骨 / 骨発生 / 硬節 / 脊索 / 変異体 / トランスジェニック / 椎骨形成 / トランスジェニックメダカ / 骨モデリング / 椎骨パターニング

Outline of Final Research Achievements

The fracture healing research revealed that generally osteoblasts are induced to enter the fracture site before the induction of osteoclasts for bone remodeling. We developed a new fracture healing model by using medaka. We fractured one side of lepidotrichia in a caudal fin ray without injuring the other soft tissues including blood vessels. Using the transgenic medaka in which osteoclasts and osteoblasts were visualized by GFP and DsRed, respectively, we found that two different types of functional osteoclasts were induced before and after osteoblast callus formation. The early-induced osteoclasts resorbed the bone fragments and the late-induced osteoclasts remodeled the callus. Both types of osteoclasts were induced near the surface on the blood vessels, while osteoblasts migrated from adjacent fin ray. Our developed medaka fracture healing model brings a new insight into the molecular mechanism for controlling cellular behaviors during the fracture healing.

Research Products

• [Journal Article] Activation of calcium signaling through Trpvl by nNOS and peroxynitrite as a key trigger of skeletal muscle hypertrophy. (2013)
  • Author(s): Ito N, et al
  • Journal Title: Nature medicine Volume: 19 Issue: 1 Pages: 101-106
  • DOI: 10.1038/nm.3019
  • Peer Reviewed
• [Journal Article] Colored medaka and zebrafish transgenics with ubiquitous and strong transgene expression driven by the medaka b-actin promoter. (2012)
  • Author(s): Yoshinari, N.
  • Journal Title: Dev. Growth Differ. Volume: 54 Pages: 818-828
  • Peer Reviewed
• [Journal Article] Periostin in dental science (2012)
  • Author(s): Takayama, I.
  • Journal Title: Jpn. Dent. Sci. Rev. Volume: 48 Issue: 2 Pages: 92-98
  • DOI: 10.1016/j.jdsr.2012.06.002
  • Peer Reviewed
• [Journal Article] Filamin C plays an essential role in the maintenance of the structural integrity of cardiac and skeletal muscles, revealed by the medaka mutant zacro (2012)
  • Author(s): 藤田深里、三橋弘明(共著)
  • Journal Title: Developmental Biology Volume: 361(1) Issue: 1 Pages: 79-89
  • DOI: 10.1016/j.ydbio.2011.10.008
  • Peer Reviewed
• [Journal Article] Osteoclasts in bone modeling, as revealed by in vivo imaging, are essential for organogenesis in fish (2011)
  • Author(s): Chatani, M., Takano, Y., Kudo, A
  • Journal Title: Dev.Biol. Volume: 360 Issue: 1 Pages: 96-109
  • DOI: 10.1016/j.ydbio.2011.09.013
  • Peer Reviewed
• [Journal Article] Periostin in fibrillogenesis for tissue regeneration : periostin actions inside and outside the cell (2011)
  • Author(s): Kudo, A
  • Journal Title: Cell.Mol.Life Sci. Volume: 68 Issue: 19 Pages: 3201-3207
  • DOI: 10.1007/s00018-011-0784-5
  • Peer Reviewed
• [Journal Article] Remodeling of actin cytoskeleton in mouse periosteal cells under mechanical loading induces periosteal cell proliferation during bone formation (2011)
  • Author(s): Sakai, D., Kii, I., Nakagawa, K., Matsumoto, H.N., Takahashi, M., Yoshida, S., Hosoya, T., Takakuda, K., Kudo, A.
  • Journal Title: PLoSONE Volume: 6 Issue: 9 Pages: e24847-e24847
  • DOI: 10.1371/journal.pone.0024847
  • Peer Reviewed
• [Journal Article] Delayed re-epithelialization in periostin-deficient mice during cutaneous wound healing (2011)
  • Author(s): Nishiyama, T., Kii, I., Kashima, T, G., Kikuchi, Y., Ohazama, A., Shimazaki, M., Fukayama, M., Kudo, A.
  • Journal Title: PLoSONE Volume: 6 Issue: 4 Pages: e18410-e18410
  • DOI: 10.1371/journal.pone.0018410
  • Peer Reviewed
• [Presentation] Induction of osteoclasts and osteoblasts during fracture healing in medaka, Oryzias latipes (2013)
  • Author(s): Kazuhiro Takeyama, Masahiro Chatani, Yoshiro Takano, Akira Kudo
  • Organizer: 第36回 日本分子生物学会 年会
  • Place of Presentation: 神戸ポートアイランド、神戸
  • Year and Date: 2013-12-03 – 2013-12-06
• [Presentation] The rankl knock-out medaka exhibits a defective phenotype of bone resorption following abnormal organogenesis together with a small number of osteoclasts regulated by RANKL-independent osteoclastogenesis (2013)
  • Author(s): 1.Masahiro Chatani, Tomoko Ishikawa, Takeshi Todo, Akira Kudo
  • Organizer: ASBMR2013 annual meeting
  • Place of Presentation: Boltimore,USA
  • Year and Date: 2013-10-04 – 2013-10-07
• [Presentation] Tooth renewal by the coupled action of osteoblasts and osteoclasts in medaka pharyngeal teeth (2013)
  • Author(s): Akiko Mantoku, Masahiro Chatani, Keiji Inohaya, Akira Kudo
  • Organizer: The 19th Japanese Medaka And Zebrafish Meeting
  • Place of Presentation: Sendai City Information & Industrial Plaza, Sendai
  • Year and Date: 2013-09-20 – 2013-09-21
• [Presentation] ifferential expression patterns of two types of medaka periostin during development and adulthood (2013)
  • Author(s): Kohei Ito, Masanobu Nishidate, Taku Akiyama, Mai Morioka, Shun Kimura, Akira Kudo
  • Organizer: 46th Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Kunibiki Messe, Matsue-City
  • Year and Date: 2013-05-28 – 2013-05-31
• [Presentation] Cyclooxygenase-2 signaling regulates osteoclast differentiation during fracture healing in medaka (2013)
  • Author(s): Kazuhiko Takeyama, Masahiro Chatani, Yoshiro Takano, Akira Kudo
  • Organizer: 46th Annual Meeting for the Japanese Society of Developmental Biologists
  • Place of Presentation: Kunibiki Messe, Matsue-City
  • Year and Date: 2013-05-28 – 2013-05-31
• [Presentation] レチノイン酸合成酵素：raldh2はメダカの脊椎骨形成に重要である。 (2012)
  • Author(s): 田崎 舞
  • Organizer: 日本動物学会
  • Place of Presentation: 大阪大学（大阪府）
• [Presentation] Medaka fused 4 mutant, which exhibits a fusion of vertebrae, encodes her7 gene. (2012)
  • Author(s): Tomizawa、S.
  • Organizer: Joint Meeting of JSDB 45 th & JSCB 64 th
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Presentation] Rald2, an enzyme involved in retinoic acid (RA) biosynthesis, is essential for osteogenesis in the medaka vertebral colum. (2012)
  • Author(s): Tasaki, M.
  • Organizer: Joint Meeting of JSDB 45 th & JSCB 64 th
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [Presentation] A huge blood cell mutant kyoho in medaka (2012)
  • Author(s): Taimatsu, K.
  • Organizer: 10 th International Conference Zebrafish Development and Genetics
  • Place of Presentation: Madison （USA）
• [Presentation] 小型魚類を用いた破骨細胞のライブイメージングと２０１２年度の宇宙実験について (2012)
  • Author(s): 茶谷昌弘
  • Organizer: 第１１回松本ボーンフォーラム
  • Place of Presentation: 信州大学（長野県）
  • Invited
• [Presentation] Medaka Bone Formation : From Foundations To Applications (2011)
  • Author(s): Akira Kudo
  • Organizer: The first Strategic Meeting for Medaka Research
  • Place of Presentation: Okazaki, Japan(招待講演)
  • Year and Date: 2011-11-23
• [Presentation] 脊椎融合メダカfu-4の解析 (2011)
  • Author(s): 富澤志帆、猪早敬二、今富徹、工藤明
  • Organizer: 第82回日本動物学会
  • Place of Presentation: 旭川
  • Year and Date: 2011-09-22
• [Presentation] 脊椎形成に異常を示すメダカraldh2変異体の解析 (2011)
  • Author(s): 田崎舞、猪早敬二、大久敬、工藤明
  • Organizer: 第82回日本動物学会
  • Place of Presentation: 旭川
  • Year and Date: 2011-09-21
• [Presentation] Eda mutants reveal that ectodysplasin and its receptor edar signaling pathway are required for fin ray formation in medaka (2011)
  • Author(s): Iida Y, Hibiya K, Inohaya K, Kudo A
  • Organizer: 17^<th> Japanese Medaka and Zebrafish Meeting
  • Place of Presentation: Mishima, Japan
  • Year and Date: 2011-09-08
• [Presentation] In vivo imaging of osteoclasts and osteoblasts in medaka fracture healing (2011)
  • Author(s): Takeyama K, Chatani, M, Kudo A
  • Organizer: 17^<th> Japanese Medaka and Zebrafish Meeting
  • Place of Presentation: Mishima, Japan
  • Year and Date: 2011-09-08
• [Presentation] メダカ骨折修復における骨芽細胞と破骨細胞のin vivoイメージング (2011)
  • Author(s): 武山和弘、茶谷昌宏、工藤明
  • Organizer: 第29回日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2011-07-28
• [Presentation] In-vivo imaging of the fracture healing process in medaka (2011)
  • Author(s): Takeyama K, Chatani, M, Inohaya K, Kudo A
  • Organizer: 第44回日本発生生物学会
  • Place of Presentation: 沖縄
  • Year and Date: 2011-05-19
• [Presentation] Mechanism of osteoclast activation under hypergravity (2011)
  • Author(s): Mantoku A, Chatani M, Kubota I, Kudo A
  • Organizer: 第44回日本発生生物学会
  • Place of Presentation: 沖縄
  • Year and Date: 2011-05-19
• [Book] Chapter 6 : Medaka Bone Development in Medaka, A Model for Organogenesis, Human Disease, and Evolution (2011)
  • Author(s): Akira Kudo
  • Total Pages: 387
  • Publisher: Springer