Osteocyte differentiation and function in bone homeostasis

• Project/Area Number: 25670773
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Morphological basic dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Nakashima Tomoki 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (00346959)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 骨生物学 / 骨恒常性 / 骨細胞

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 osteocyte differentiation and function, we performed a genome-wide screening of osteocytes and establishment of osteocytogenesis assay system.

Research Products

• [Journal Article] IL-17-producing γδ T cells enhance bone regeneration (2016)
  • Author(s): Ono T, et al.
  • Journal Title: Nat Commun Volume: 7 Issue: 1 Pages: 10928-10928
  • DOI: 10.1038/ncomms10928
  • Peer Reviewed / Open Access
• [Journal Article] RANKL inhibition prevents autoimmune inflammation in the central nervous system (2015)
  • Author(s): Guerrini M.M, Okamoto K, Komatsu N, Sawa S, Danks L, Penninger J.M, Nakashima T, Takayanagi H.
  • Journal Title: Immunity Volume: 43 Issue: 6 Pages: 1174-1185
  • DOI: 10.1016/j.immuni.2015.10.017
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation. (2015)
  • Author(s): Danks L, Komatsu N, Guerrini MM, Sawa S, Armaka M, Kollias G, Nakashima T, Takayanagi H.
  • Journal Title: Annals of the Rheumatic Diseases Volume: - Issue: 6 Pages: 207137-207137
  • DOI: 10.1136/annrheumdis-2014-207137
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Bone remodeling and alveolar bone homeostasis (2015)
  • Author(s): Nakashima T
  • Journal Title: Clin Calcium Volume: 25 Pages: 1220-8
• [Journal Article] Amazing function of osteocyte (2015)
  • Author(s): Nakashima T
  • Journal Title: Clin Calcium Volume: 25 Pages: 899-905
• [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
• [Presentation] セマフォリンによる骨リモデリングの制御 (2016)
  • Author(s): 中島友紀
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィッコ横浜(横浜)
  • Year and Date: 2016-03-09
  • Invited
• [Presentation] RANKL Biology (2015)
  • Author(s): 中島友紀
  • Organizer: 日本リウマチ学会ベーシックリサーチカンファレン
  • Place of Presentation: 東京大学鉄門記念講堂（東京）
  • Year and Date: 2015-10-15
  • Invited
• [Presentation] 骨リモデリングの制御機構 (2015)
  • Author(s): 中島友紀
  • Organizer: 第57回歯科基礎医学会
  • Place of Presentation: 朱鷺メッセ（新潟）
  • Year and Date: 2015-09-13
  • Invited
• [Presentation] 骨リモデリングの制御機構の解明 (2015)
  • Author(s): 中島友紀
  • Organizer: 第33回 日本骨代謝学会
  • Place of Presentation: 京王プラザホテル（東京）
  • Year and Date: 2015-07-24
  • Invited
• [Presentation] 骨破壊を司る破骨細胞の制御機構 (2015)
  • Author(s): 中島友紀
  • Organizer: 第1回骨免疫学会
  • Place of Presentation: ホテルブリーズベイマリーナ（沖縄）
  • Year and Date: 2015-07-02
  • Invited
• [Presentation] Regulation of bone remodeling (2015)
  • Author(s): Nakashima T
  • Organizer: 3nd Seoul Symposium on Bone Health KSBMR-JSBMR joint symposium
  • Place of Presentation: 韓国（Seoul）
  • Year and Date: 2015-05-27
  • Int'l Joint Research / Invited
• [Presentation] 骨を基軸とした多臓器連関 (2015)
  • Author(s): 中島友紀
  • Organizer: 12th Asia Congress of Nutrition/第69回日本栄養・食料学会
  • Place of Presentation: パシフィッコ横浜(横浜)
  • Year and Date: 2015-05-16
  • Int'l Joint Research / Invited
• [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] 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] Semaphorin ; Semaphorins in bone homeostasis. (2015)
  • Author(s): Hayashi M, Nakashima T, Takayanagi H
  • Publisher: Springer New York, Editor Atsushi Kumanogoh
• [Book] Semaphorins (2015)
  • Author(s): Hayashi M, Nakashima T, Takayanagi H.
  • Publisher: Springer New York