Analysis of the regulation of bone metabolism by the pool of osteoclast precursors

• Project/Area Number: 22791804
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Matsumoto Dental University
• Principal Investigator: MIZOGUCHI Toshihide 松本歯科大学, 総合歯科医学研究所, 講師 (90329475)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 破骨細胞前駆細胞(QOP) / RANK / c-Fms / c-Fos / 破骨細胞 / Fms / c-FOS / ヒドロキシウレア / RANKL / QOP / 骨芽細胞 / 増殖 / BMP

Research Abstract

We examined the characteristics of osteoclast precursors in vivo, and found that the precursor are specific myeloid cells, not common monocytes or macrophages. We named these precursors "cell cycle-arrested quiescent osteoclast precursors(QOP). QOP differentiate into osteoclasts without cell cycle progression. In the present study, I revealed that (1) QOP circulate in the blood and settle in the bone in response to bone resorption stimuli, (2) the expression level of RANK is up-regulated by M-CSF(CSF1) in the QOP along the bone surface, and the expression of c-Fos in the QOP is also necessary for the up-regulation of RANK.

Research Products

• [Journal Article] c-Fos plays an essential role in the up-regulation of RANK expression in osteoclast precursors within the bone microenvironment (2012)
  • Author(s): Arai A, Mizoguchi T(他8名)
  • Journal Title: J Cell Sci Volume: (in press)
  • Peer Reviewed
• [Journal Article] Carbon Nanotubes Induce Bone Calcification by Bidirection with Osteoblasts (2012)
  • Author(s): Shimizu M(1), Mizoguchi T(3), (他20名)
  • Journal Title: Adv Mater Volume: 24 Pages: 2176-2185
  • Peer Reviewed
• [Journal Article] Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis (2012)
  • Author(s): Maeda K(1), Mizoguchi T(6), (他13名)
  • Journal Title: Nat Med Volume: 18 Pages: 405-412
  • Peer Reviewed
• [Journal Article] Tetracyclines convert the osteoclastic-differentiation pathway of progenitor cells to produce dendritic cell-like cells (2012)
  • Author(s): Kinugawa S(1), Mizoguchi T(4), (他9名)
  • Journal Title: J Immunol Volume: 188 Pages: 1772-1781
  • Peer Reviewed
• [Journal Article] Daily administration of eldecalcitol(ED-71), an active vitamin D analog, increase bone mineral density by suppressing RANKL expression in mouse trabecular bone (2012)
  • Author(s): Harada S(1). Mizoguchi T(equal contribution)(2), (他9名), Kobayashi Y, Nakamichi Y, Takeda S, Takahashi F, Saito H, Yasuda H, Udagawa N, Suda T, Takahashi N.
  • Journal Title: J Bone Miner Res Volume: 27 Pages: 461-473
  • Peer Reviewed
• [Journal Article] Polarized osteoclasts put marks of tartate-resistant acid phosphatase on dentine slices-a simple method for identifying polarized osteoclasts (2012)
  • Author(s): Nakayama T, et al
  • Journal Title: Bone Volume: 49 Issue: 6 Pages: 1331-1339
  • DOI: 10.1016/j.bone.2011.09.045
  • Peer Reviewed
• [Journal Article] Daily administration of Eldecalcitol (ED-71), an active vitamin Danalog, increases bone mineral density by suppressing RANKL expression in mouse trabecular bone (2012)
  • Author(s): Harada S, et al
  • Journal Title: J Bone Miner Res Volume: 27 Issue: 2 Pages: 461-473
  • DOI: 10.1002/jbmr.555
  • Peer Reviewed
• [Journal Article] Carbon nanotubes induce bone calcification by bidirectional interaction with osteoblasts (2012)
  • Author(s): Shimizu M, Kobayashi Y, Mizoguchi T, Nakamura H, Kawahara I, Narita N, Usui Y, Aoki K, Hara K, Haniu H, Ogihara N, Ishigaki N, Nakamura K, Kato H, Kawakubo M, Dohi Y, Taruta S, Kim YA, Endo M, Ozawa H, Udagawa N, Takahashi N, Saito N
  • Journal Title: Advanced Materials Volume: 24 Issue: 16 Pages: 2176-2185
  • DOI: 10.1002/adma.201103832
  • Peer Reviewed
• [Journal Article] c-Fos plays an essential role in the up-regulation of RANK expression in osteoclast precursors within the bone microenvironment (2012)
  • Author(s): Arai A, et al
  • Journal Title: J Cell Sci Volume: (印刷中) Pages: 2910-2917
  • DOI: 10.1242/jcs.099986
  • Peer Reviewed
• [Journal Article] Polarized osteoclasts put marks of tartrate-resistant acid phosphatase on dentin slices-A simple method for identifying polarized osteoclasts (2011)
  • Author(s): Nakayama T(1). Mizoguchi T(2), (他10名)
  • Journal Title: Bone Volume: 49 Pages: 1331-1339
  • Peer Reviewed
• [Journal Article] Frontiers in Vitamin D ; Basic Research and Clinical Application. Inhibitory Effects of Eldecalcitol, an Active Vitamin D Derivative, on Bone Resorption in Vivo (2011)
  • Author(s): Harada S(1), Mizoguchi T(2), (他1名)
  • Journal Title: Clin Calcium Volume: 11 Pages: 1675-1682
• [Journal Article] Lineage-committed osteoclast precursors circulating in blood and settle down into bone (2011)
  • Author(s): Muto M(1). Mizoguchi T(equal contribution)(2), (他11名)
  • Journal Title: J Bone Miner Res Volume: 26 Pages: 2978-2990
  • Peer Reviewed
• [Journal Article] RANKL signaling and bone diseases. Quiescent osteoclast precursors and RANKL signaling (2011)
  • Author(s): Mizoguchi T.
  • Journal Title: Clin Calcium Volume: 8 Pages: 1187-1192
• [Journal Article] Identification of cell cycle-arrested quiescent osteoclast precursors in vivo (2010)
  • Author(s): Takahashi N(1), Muto A, Arai A, Mizoguchi T(4).(他2名)
  • Journal Title: Adv Exp Med Biol Volume: 658 Pages: 21-30
  • Peer Reviewed
• [Journal Article] Identification of cell cycle-arrested quiescent osteoclast precursors in vivo. (2010)
  • Author(s): Takahashi N, et al.
  • Journal Title: Adv Exp Med Biol. Volume: 658 Pages: 21-30
  • Peer Reviewed
• [Presentation] Daily administration of Eldecalcitol(ED-71), an active vitamin D analog, increases bone mineral density by suppressing RANKL expression in mouse trabecular bone (2011)
  • Author(s): Harada S
  • Organizer: 33^<th> American Society for Bone and Mineral Research(ASBMR) Annual Meeting
  • Place of Presentation: サンディエゴ・USA
  • Year and Date: 2011-10-16
• [Presentation] c-Fos plays an essential role in up-regulation of RANK expression in osteoclast precursors (2011)
  • Author(s): Arai A
  • Organizer: IOF Regionals 2^<nd> Asia-Pacific Osteoporosis and Bone Meeting ANZBMS Annual Scientific Meeting, with JSBMR
  • Place of Presentation: ゴールドコースト・オーストラリア
  • Year and Date: 2011-09-06
• [Presentation] BMP-induced ectopic bone formation in c-Fos-deficient mice (2011)
  • Author(s): Nakamura M
  • Organizer: IOF Regionals 2nd Asia-Pacific Osteoporosis and Bone Meeting ANZBMS Annual Scientific Meeting, with JSBMR
  • Place of Presentation: ゴールドコースト・オーストラリア
  • Year and Date: 2011-09-05
• [Presentation] c-Fos遺伝子欠損マウスを用いたBMP誘導性異所性骨形成に関する解析 (2011)
  • Author(s): 中村みどり
  • Organizer: 日本骨代謝学会学術集会(第29回)
  • Place of Presentation: 大阪・大阪国際会議場
  • Year and Date: 2011-07-30
• [Presentation] 生体内における破骨細胞分化機構の解明-M-CSFはc-Fosを介して破骨細胞前駆細胞のRANK発現を上昇する- (2011)
  • Author(s): 荒井敦
  • Organizer: 日本骨代謝学会学術集会(第29回)
  • Place of Presentation: 大阪・大阪国際会議場
  • Year and Date: 2011-07-29
• [Presentation] Eldecalcitol(ED-71)は海綿骨におけるRANKLの発現を抑制し、骨密度を増加させる (2011)
  • Author(s): 原田卓
  • Organizer: 日本骨代謝学会学術集会(第29回)
  • Place of Presentation: 大阪・大阪国際会議場
  • Year and Date: 2011-07-29
• [Presentation] 破骨細胞の極性化指標TRAP-markは分泌痕跡である (2011)
  • Author(s): 中山貴裕
  • Organizer: 日本骨代謝学会学術集会(第29回)
  • Place of Presentation: 大阪・大阪国際会議場
  • Year and Date: 2011-07-29
• [Presentation] in vivoにおける破骨細胞分化機構の解析-M-CSFはc-Fosを介し前駆細胞のRANKを上昇する (2011)
  • Author(s): 荒井敦
  • Organizer: 松本歯科大学学会例会(第72回)
  • Place of Presentation: 長野・松本歯科大学
  • Year and Date: 2011-07-09
• [Presentation] 簡便な破骨細胞の極性化解析法の確立 (2010)
  • Author(s): 中山貴裕
  • Organizer: 日本骨代謝学会学術集会(第28回)
  • Place of Presentation: 東京・京王プラザホテル
  • Year and Date: 2010-07-23
• [Presentation] Isolation and characterization of osteoclast precursors in vivo (2010)
  • Author(s): 溝口利英
  • Organizer: Bone Research Seminar
  • Place of Presentation: 東京コンファレンスセンター(東京)
  • Year and Date: 2010-02-19
• [Presentation] In vivoにおける破骨細胞前駆細胞の同定と分化機構の解析 (2010)
  • Author(s): 溝口利英
  • Organizer: Osteoimmunology Forum(第7回)
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2010-02-06