Reglation of mineralization by osteocyte

• Project/Area Number: 24390412
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NAKAHSIMA Tomoki 東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (00346959)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2012: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: 骨代謝学 / 骨細胞 / ミネラリゼーション / 骨溶解

Outline of Final Research Achievements

Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "bone remodeling" is important not only for normal bone mass and strength, but also for mineral homeostasis. Osteocytes, the most numerous and least well studied bone cells, are stellate-shaped cells enclosed within the bone lacuno-canalicular network of bone. Based on the osteocyte location within the bone matrix and the cellular morphology, it is proposed that osteocytes potentially contribute to the regulation of bone remodeling in response to mechanical and endocrine stimuli. To identify the regulation factor of bone remodeling and mineralization, we performed a genome-wide screening of osteocytes, and in vivo analysis of bone disease model and gene targeting mice.

Research Products

• [Journal Article] Global epigenomic analysis indicates protocadherin-7 activates osteoclastogenesis by promoting cell-cell fusion (2014)
  • Author(s): Nakamura H, Nakashima T, Hayashi M, Izawa N, Yasui T, Aburatani H, Tanaka S, Takayanagi H.
  • Journal Title: Biochem Biophys Res Commun Volume: 455 Issue: 3-4 Pages: 305
  • DOI: 10.1016/j.bbrc.2014.11.009
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Peyer's patches and mesenteric lymph nodes cooperatively promote enteropathy in a mouse model of food allergy. (2014)
  • Author(s): Nakajima-Adachi, H., Kikuchi, A., Fujimura, Y., Shibahara, K., Makino, T., Goseki-Sone, M., Kihara-Fujioka, M., Nochi, T., Kurashima, Y., Igarashi, O., Yamamoto, M., Kunisawa, J., Toda, M., Kaminogawa, S., Sato, R., Kiyono, H., and Hachimura, S.
  • Journal Title: PLoS One. Volume: 9 Issue: 9 Pages: 108294-108294
  • DOI: 10.1371/journal.pone.0108294
  • Peer Reviewed / Open Access
• [Journal Article] Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis. (2014)
  • Author(s): Komatsu, N., Okamoto, K., Sawa, S., Nakashima, T., Oh-hora, M., Kodama, T., Tanaka, S., Bluestone, JA. and Takayanagi, H.
  • Journal Title: Nature Medicine Volume: 20 Issue: 1 Pages: 62-68
  • DOI: 10.1038/nm.3432
  • Peer Reviewed / Open Access
• [Journal Article] RANKLの多彩な作用 (2014)
  • Author(s): 中島友紀
  • Journal Title: 実験医学（増刊） Volume: 32 Pages: 43-52
• [Journal Article] 骨細胞による骨制御 (2014)
  • Author(s): 中島友紀
  • Journal Title: 腎と骨代謝 Volume: 27 Pages: 136-146
• [Journal Article] 乳癌の骨転移病変とRANKL (2014)
  • Author(s): 中島友紀
  • Journal Title: 腎と骨代謝 Volume: 27 Pages: 15-23
• [Journal Article] Osteocyte control of osteoclastogenesis. (2013)
  • Author(s): O'Brien CA, Nakashima T, Takayanagi H.
  • Journal Title: Bone Volume: 54 Issue: 2 Pages: 258-263
  • DOI: 10.1016/j.bone.2012.08.121
  • Peer Reviewed
• [Journal Article] ストレスと骨の細胞間コミュニケーション (2013)
  • Author(s): 中島友紀
  • Journal Title: CLINICAL CALCIUM Volume: 23 Pages: 1595-1603
• [Journal Article] 骨細胞による骨吸収制御 (2013)
  • Author(s): 中島友紀
  • Journal Title: THE BONE Volume: 27 Pages: 49-57
• [Journal Article] New insights into osteoclastogenic signaling mechanisms (2012)
  • Author(s): Nakashima T et.ai.
  • Journal Title: Trends Endocrinol Metab Volume: 23 Issue: 11 Pages: 582-590
  • DOI: 10.1016/j.tem.2012.05.005
  • Peer Reviewed
• [Journal Article] Osteoprotection by semaphorin 3A (2012)
  • Author(s): Mikihito Hayashi, Tomoki Nakashima, Masahiko Taniguchi, Tatsuhiko Kodama, Atsushi Kumanogoh and Hiroshi Takayanagi
  • Journal Title: Nature Volume: 485 Issue: 7396 Pages: 69-74
  • DOI: 10.1038/nature11000
  • Peer Reviewed
• [Journal Article] RANK and RANKL (2012)
  • Author(s): Nakashima T, et.al.
  • Journal Title: Encyclopedia of Signaling Molecules Pages: 1581-1589
  • 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] 骨代謝における骨細胞の新たな役割 (2012)
  • Author(s): 中島友紀
  • Journal Title: Medical Practice Volume: 29 Pages: 1925-1928
• [Journal Article] 骨細胞による骨恒常性の制御 (2012)
  • Author(s): 中島友紀
  • Journal Title: リウマチ科 Volume: 48 Pages: 352-361
• [Journal Article] 骨細胞による骨リモデリング制御 (2012)
  • Author(s): 中島友紀
  • Journal Title: THE BONE Volume: 26 Pages: 5-10
• [Journal Article] 骨細胞による骨吸収制御 (2012)
  • Author(s): 中島友紀
  • Journal Title: CLINICAL CALCIUM Volume: 22 Pages: 85-96
• [Journal Article] 骨免疫学からみたRA治療の新展開 (2012)
  • Author(s): 中島友紀
  • Journal Title: 最新医学 Volume: 62 Pages: 203-211
• [Presentation] RANKL Biology (2014)
  • Author(s): 中島友紀
  • Organizer: 第32回日本骨代謝学会 日韓合同シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-26
  • Invited
• [Presentation] 炎症と骨破壊 (2014)
  • Author(s): 中島友紀
  • Organizer: 第32回日本骨代謝学会 日本リウマチ学会合同シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-25
  • Invited
• [Presentation] 骨と運動器の連環システム (2014)
  • Author(s): 中島友紀
  • Organizer: 第32回日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-24
  • Invited
• [Presentation] Osteocyte-derived RANKL in bone remodeling (2012)
  • Author(s): Tomoki Nakashima
  • Organizer: American Socuety for Bone and Mineral Research 2012 Annual Meeting
  • Place of Presentation: Minneapolis USA
  • Year and Date: 2012-09-13
• [Presentation] Osteoprotection by semaphoring 3A (2012)
  • Author(s): Tomoki Nakashima
  • Organizer: 22^(nd) Annual Scientific Meeting ANZBMS and Asia-Pacific Bone and Mineral Research Meeting
  • Place of Presentation: Australia(招待講演)
  • Year and Date: 2012-09-13
• [Presentation] 骨細胞による破骨細胞分化の制御機構 (2012)
  • Author(s): 中島友紀
  • Organizer: 第30回日本骨代謝学会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2012-07-21
• [Presentation] 骨リモデリングの制御機構の解明 (2012)
  • Author(s): 中島友紀
  • Organizer: 第30回日本骨代謝学会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2012-07-20
• [Presentation] 骨リモデリングの制御機構の解明 (2012)
  • Author(s): 中島友紀
  • Organizer: 第33回日本炎症・再生医学会
  • Place of Presentation: 福岡(招待講演)
  • Year and Date: 2012-07-05
• [Presentation] 骨リモデリングの制御機構の解明 (2012)
  • Author(s): 中島友紀
  • Organizer: 第54回日本老年医学会学術集会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2012-06-29
• [Presentation] 骨リモデリングの制御機構の解明 (2012)
  • Author(s): 中島友紀
  • Organizer: 第12回日本抗加齢医学会総会
  • Place of Presentation: 横浜(招待講演)
  • Year and Date: 2012-06-24
• [Presentation] 骨リモデリングの制御機構の解明 (2012)
  • Author(s): 中島友紀
  • Organizer: 第66回日本口腔科学会学術集会
  • Place of Presentation: 広島(招待講演)
  • Year and Date: 2012-05-16
• [Presentation] RANKLと骨免疫学 (2012)
  • Author(s): 中島友紀
  • Organizer: 第56回日本リウマチ学会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2012-04-28
• [Presentation] 骨細胞による骨吸収制御機構
  • Author(s): 中島友紀
  • Organizer: 第55回歯科基礎医学会
  • Place of Presentation: 岡山(岡山コンベンションセンター)
  • Invited
• [Presentation] RANKLと骨疾患
  • Author(s): 中島友紀
  • Organizer: 国際骨代謝学会・日本骨代謝学会第2回 合同国際会議
  • Place of Presentation: 神戸（神戸コンベンションセンター・神戸ポートピアホテル）
  • Invited
• [Presentation] Regulation of bone remodeling by osteocytes.
  • Author(s): 中島友紀
  • Organizer: 第22回国際リウマチシンポジウム/第57回日本リウマチ学会
  • Place of Presentation: 京都（国立京都国際会館）
  • Invited
• [Book] Semaphorins (2015)
  • Author(s): Hayashi M, Nakashima T, Takayanagi H.
  • Publisher: Springer New York