Analysis of roles of Wnt5a in alveolar bone remodeling, and their application for orthodontic tooth movement.

• Project/Area Number: 21390551
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthodontic/Pediatric dentistry
• Research Institution: Matsumoto Dental University
• Principal Investigator: KOBAYASHI Yasuhiro 松本歯科大学, 総合歯科医学研究所, 准教授 (20264252)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Naoyuki 松本歯科大学, 総合歯科医学研究所, 教授 (90119222) ; HIRAGA Tohru 松本歯科大学, 歯学部, 准教授 (70322170) ; YAMASHITA Teruhito 松本歯科大学, 総合歯科医学研究所, 講師 (90302893) ; MIZOGUCHI Toshihide 松本歯科大学, 総合歯科医学研究所, 講師 (90329475)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2011: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2010: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2009: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: 歯科矯正学 / 破骨細胞 / Wnt5a / 骨芽細胞特異的遺伝子欠損 / 骨吸収 / 骨形成 / 歯の移動 / 骨代謝回転 / 加齢 / Wnt / 歯槽骨 / コンディショナルノックアウト

Research Abstract

Wnt5a secreted from osteoblasts binds to Ror2 receptors in osteoclast precursors. Ror2-mediated signals promote RANK expression in osteoclast precursors, thereby enhancing RANKL-induced osteoclastogenesis. In addition, Wnt5a enhances osteoblastic differentiation and inhibits adipogenesis. Together, Wnt5a regulates osteoclastogenesis and osteogenesis in alveolar bone remodeling.

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, Harada S, Kobayashi Y, Nakamichi Y, Yasuda H, Penninger JM, Yamada K, Udagawa N, Takahashi N
  • Journal Title: J. Cell Sci
  • 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] Wntによる骨代謝制御機構 (2012)
  • Author(s): 小林泰浩
  • Journal Title: The Bone Volume: 26 Pages: 151-159
• [Journal Article] Wnt5a-Ror2 signaling between osteoblasts and osteoclast precursors enhances osteoclastogenesis (2012)
  • Author(s): Maeda, K., Kobayashi, Y., Udagawa, N., Uehara, S., Ishihara, A., Mizoguchi, T., Kikuchi, Y., Takada, I., Kato, S., Kani, S., Nishita, M., Marumo, K., Martin, T.J., Minami, Y., Takahashi, N.
  • Journal Title: Nat.Med. Volume: (印刷中) Issue: 3 Pages: 405-12
  • DOI: 10.1038/nm.2653
  • 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] Tetracyclines convert the osteoclastic-differentiation pathway of orogenitor cells to produce dendritic cell-like cells (2012)
  • Author(s): Kinugawa S, et al
  • Journal Title: J Immunol Volume: 188 Issue: 4 Pages: 1772-1781
  • DOI: 10.4049/jimmunol.1101174
  • Peer Reviewed
• [Journal Article] Thy-1-positive cells in the subodontoblastic layer possess high potential to differentiate into hard tissue-forming cells. (2012)
  • Author(s): Hosoya A, Hiraga T, Ninomiya T, Yukita A, Yoshiba K, Yoshiba N, Takahashi M, Ito S, Nakamura H.
  • Journal Title: Histochem Cell Biol Volume: 137(6) Issue: 6 Pages: 733-42
  • DOI: 10.1007/s00418-012-0928-1
  • 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, Mizoguchi T, Uehara S, Yamashita T, Kawahara I, Kobayashi Y, Moriyama Y, Kurihara S, Sahara N, Ozawa H, Udagawa N, Takahashi N
  • Journal Title: Bone Volume: 49 Pages: 1331-1339
  • URL: http://dx.doi.org/10.1016/j.bone.2011.09.045
  • Peer Reviewed
• [Journal Article] Lineage-Committed Osteoclast Precursors Circulate in Blood and Settle Down Into Bone (2011)
  • Author(s): Muto, A, Mizoguchi, T, Udagawa, N., Ito, S, Kawahara, I, Abiko, Y, Arai, A., Harada, S., Kobayashi, Y., Nakamichi, Y, Penninger, JM, Noguchi, T, Takahashi, N.
  • Journal Title: Journal of Bone and Mineral Research Volume: 26 Issue: 12 Pages: 2978-2990
  • DOI: 10.1002/jbmr.490
  • Peer Reviewed
• [Journal Article] Prostaglandin E(2) receptor EP(4)-selective agonist(ONO-4819) increases bone formation by modulating mesenchymal cell differentiation (2011)
  • Author(s): Ninomiya T, Hosoya A, Hiraga T, Koide M, Yamaguchi K, Oida H, Arai Y, Sahara N, Nakamura H, Ozawa H
  • Journal Title: Eur. J. Pharmacol Volume: 650 Pages: 396-402
  • URL: http://dx.doi.org/10.1016/j.ejphar.2010.10.021
  • Peer Reviewed
• [Journal Article] Side population in MDA-MB-231 human breast cancer cells exhibits cancer stem cell-like properties without higher bone-metastatic potential. (2011)
  • Author(s): Hiraga T, Ito S, Nakamura H.
  • Journal Title: Oncol Rep Volume: 25(1) Issue: 1 Pages: 289-96
  • DOI: 10.3892/or_00001073
  • Peer Reviewed
• [Journal Article] Regulatory mechanism of osteoclastogenesis by RANKL and Wnt signals (2011)
  • Author(s): Takahashi N, Maeda K, Ishihara A, Uehara S, Kobayashi Y
  • Journal Title: Front. Biosci Volume: 16 Pages: 21-30
  • URL: http://dx.doi.org/10.2741/3673
  • Peer Reviewed
• [Journal Article] Regulatory mechanism of osteoclastogenesis by RANKL and Wnt signals. (2011)
  • Author(s): Takahashi N, et.al.
  • Journal Title: Front Biosci Volume: 16 Pages: 21-30
  • Peer Reviewed
• [Journal Article] Identification of osteoclasts in culture. (2011)
  • Author(s): Udagawa N, et.al.
  • Journal Title: Methods Mol Biol. Volume: 690 Pages: 273-284
  • Peer Reviewed
• [Journal Article] Alisol-B, a novel phyto-steroid, suppresses the RANKL-induced osteoclast formation and prevents bone loss in mice (2010)
  • Author(s): Lee JW, Kobayashi Y, Nakamichi Y, Udagawa N, Takahashi N, Im NK, Seo HJ, Jeon WB, Yonezawa T, Cha BY, Woo JT.
  • Journal Title: Biochem. Pharmacol Volume: 80 Pages: 352-361
  • URL: http://dx.doi.org/10.1016/j.bcp.2010.04.014
  • Peer Reviewed
• [Journal Article] Acid activation of Trpv1 leads to an up-regulation of calcitonin gene-related peptide expression in dorsal root ganglion neurons via the CaMK-CREB cascade: a potential mechanism of inflammatory pain. (2010)
  • Author(s): Nakanishi M, Hata K, Nagayama T, SakuraiT, Nishisho T, Wakabayashi H, Hiraga T, Ebisu S, Yoneda T.
  • Journal Title: Mol Biol Cell Volume: 21(15) Issue: 15 Pages: 2568-77
  • DOI: 10.1091/mbc.e10-01-0049
  • Peer Reviewed
• [Journal Article] Administration of the bisphosphonate zoledronic acid during tooth development inhibits tooth eruption and formation and induces dental abnormalities in rats. (2010)
  • Author(s): Hiraga T, Ninomiya T, Hosoya A, Nakamura H.
  • Journal Title: Calcif Tissue Int Volume: 86(6) Issue: 6 Pages: 502-10
  • DOI: 10.1007/s00223-010-9366-z
  • Peer Reviewed
• [Journal Article] Alisol-B, a novel phyto-steroid, suppresses the RANKL-induced osteoclast formation and prevents bone loss in mice. (2010)
  • Author(s): Lee JW, et.al.
  • Journal Title: Biochem Pharmacol. Volume: 80 Pages: 352-361
  • Peer Reviewed
• [Journal Article] Alisol-B, a novel phyto-steroid, suppressed the RANKL-induced osteoclast formation and prevents bone loss in mice. (2010)
  • Author(s): Lee JW, et al.
  • Journal Title: Biochem Pharmacol. (印刷中)
  • Peer Reviewed
• [Journal Article] Action of RANKL and OPG for osteoclastogenesis (2009)
  • Author(s): Kobayashi Y, Udagawa N, Takahashi N
  • Journal Title: Crit. Rev. Eukaryot. Gene Expr Volume: 19 Pages: 61-72
  • Peer Reviewed
• [Journal Article] Diphenylhydantoin inhibits osteoclast differentiation and function through suppression of NFATc1 signaling. (2009)
  • Author(s): Koide M, et al.
  • Journal Title: J Bone Miner Res. 24 Pages: 1469-1480
  • Peer Reviewed
• [Presentation] Wnt5a-Ror2シグナルによる破骨細胞分化制御機構 (2012)
  • Author(s): 小林泰浩
  • Organizer: 第10回口腔医科学フロンティア学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2012-03-03
• [Presentation] Wnt5a-Ror2シグナルによる破骨細胞分化制御機構 (2012)
  • Author(s): 小林泰浩
  • Organizer: 第10回口腔医科学フロンティア学術集会
  • Place of Presentation: 大阪大学・歯学部(吹田市)
  • Year and Date: 2012-03-01
• [Presentation] Wntシグナルによる破骨細胞分化調節機構の解析 (2010)
  • Author(s): 小林泰浩、溝口利英、上原俊介、高橋直之、宇田川信之
  • Organizer: 第71回松本歯科大学学会例会
  • Place of Presentation: 塩尻
  • Year and Date: 2010-11-13
• [Presentation] Wnt5aはRANKの発現を亢進し、破骨細胞分化を促進する (2010)
  • Author(s): 小林泰浩, 前田和洋、上原俊介、高田伊知郎、加藤茂明、丸毛啓史、宇田川信之、高橋直之
  • Organizer: 第28回日本骨代謝学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-21
• [Presentation] 漢方牛蒡子由来のアルクチゲニンは破骨細胞の機能と分化を抑制する (2010)
  • Author(s): 山下照仁、上原俊介、小林泰浩、宇田川信之、高橋直之
  • Organizer: 第28回日本骨代謝学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-21
• [Presentation] Ror2-mediated noncanonical Wnt signaling enhances RANKL-induced osteoclast formation in physiological and pathological conditions (2010)
  • Author(s): Kobayashi Y, et al
  • Organizer: 3^<rd> International conference on osteoimmun ology
  • Place of Presentation: Santorini, Greece
  • Year and Date: 2010-06-25
• [Presentation] Ror2-mediated noncanonical Wnt signaling enhances RANKL-induced osteoclast formation in physiological and pathological conditions (2010)
  • Author(s): Kobayayahi Yasuhiro
  • Organizer: 3rd International Conference on Osteoimmunology : Interactions of the Immune and Skeletal systems
  • Place of Presentation: Nomikos Conference Center, Santorini
  • Year and Date: 2010-06-22
• [Presentation] Ror2-mediated noncanonical Wnt signaling enhances RANKL-induced osteoclast formation in physiological and pathological conditions (2009)
  • Author(s): 小林泰浩
  • Organizer: 第26回 内藤カンファレンスOsteobiology
  • Place of Presentation: 淡路夢舞台国際会議場
  • Year and Date: 2009-11-05
• [Presentation] Ror2-mediated noncanonical Wnt signaling stimulates physiological and pathological osteoclastogenesis in a cell autonomous manner (2009)
  • Author(s): Kobayashi Y
  • Organizer: 第6回Bone Biology Forum
  • Place of Presentation: 裾野
  • Year and Date: 2009-08-22
• [Presentation] Ror2-mediated noncanonical Wnt signaling stimulates physiological and pathological osteoclastogenesis in a cell autonomous manner (2009)
  • Author(s): 小林泰浩
  • Organizer: 第6回 Bone Biology Forum
  • Place of Presentation: 帝人富士教育研修所
  • Year and Date: 2009-08-22
• [Presentation] 炎症性骨疾患におけるWntの役割 (2009)
  • Author(s): 小林泰浩
  • Organizer: 第27回日本骨代謝学会、ミニシンポジウムOsteoimmunology 11
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-25
• [Presentation] 炎症性骨疾患におけるWntシグナルの役割 (2009)
  • Author(s): 小林泰浩
  • Organizer: 第27回 日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-07-25
• [Book] Identification of osteoclasts in culture (2011)
  • Author(s): Udagawa N, Yamashita T, Kobayashi Y, Takahashi N, Nicole I zur Nieden
  • Publisher: Springer Science