Role of Wnt-Ror2 signals in ruffled border formation in osteoclasts

• Project/Area Number: 22659339
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Matsumoto Dental University
• Principal Investigator: TAKAHASHI Naoyuki 松本歯科大学, 総合歯科医学研究所, 教授 (90119222)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Yasuhiro 松本歯科大学, 総合歯科医学研究所, 準教授 (20264252) ; UEHARA Shunsuke 松本歯科大学, 歯学部, 助教 (90434480)
• Co-Investigator(Renkei-kenkyūsha): UDAGAWA Nobuyuki 松本歯科大, 歯学部, 教授 (70245801)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,190,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 口腔生化学 / 破骨細胞 / Wnt非古典経路 / 極性化 / 波上縁 / Wnt5a-Ror2シグナル / 低分子量Gタンパク質 / Wnt / Rho

Research Abstract

The role of Wnt5a-Ror2 signals in osteoclast function was studied. (1) Bone-resorbing activities of osteoclasts derived from Wnt5a-deficient mice and from Ror2 deficient mice were lower than that of wild-type(WT) osteoclasts. (2) Wnt5a activated Rho, a small G protein, in WT osteoclasts but not in Ror2-deficient osteoclasts. (3) When active Rho was transfected into Ror2-deficient osteoclasts, the bone-resorbing activity was recovered. Thus, Wnt5a-Ror2 signals play important roles in osteoclast function through a Rho-dependent mechanism.

Research Products

• [Journal Article] Regulation of Osteoclast Function (2012)
  • Author(s): Nakamura I, Takahashi N, Jimi E, Udagawa N, Suda T
  • Journal Title: Mod Rheumatol Volume: 22(2) Pages: 167-177
  • NAID: 10030614771
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21953286
  • 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] 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] 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] 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] 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] Increased bone mass in mice after a single injection of an anti-RANKL neutralizing antibody : evidence for a bone anabolic effect of PTH in mice with few osteoclasts (2011)
  • Author(s): Furuya Y, et al
  • Journal Title: J Biol Chem Volume: 286 Issue: 42 Pages: 37023-37031
  • DOI: 10.1074/jbc.m111.246280
  • Peer Reviewed
• [Journal Article] Hyergravity suppresses bone resorption in ovariectomized rat (2011)
  • Author(s): Ikawa T, et al
  • Journal Title: Adv Space Res Volume: 47 Issue: 7 Pages: 1214-1224
  • DOI: 10.1016/j.asr.2010.12.004
  • 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] 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(6) Pages: 1331-1339
  • 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://www.ncbi.nlm.nih.gov/pubmed/21196156
  • 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
  • DOI: 10.1007/978-1-60761-962-8_18
  • ISBN: 9781607619611, 9781607619628
  • 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
• [Journal Article] Osteoclastic bone resorption induced by innate immune responses. (2010)
  • Author(s): Koide M, et al.
  • Journal Title: Periodontol 2000 Volume: 54 Pages: 235-246
  • Peer Reviewed
• [Journal Article] Function of OPG as a traffic regulator for RANKL is crucial for controlled osteoclastogenesis. (2010)
  • Author(s): Aoki S, et al.
  • Journal Title: J Bone Miner Res Volume: 25 Pages: 1907-1921
  • Peer Reviewed
• [Journal Article] Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in CSF-1^<op/op> mice
  • Author(s): Nakamichi Y, Mizoguchi T, Arai A, Kobayashi Y, Sato M, Penninger JM, Yasuda H, Kato S, DeLuca HF, Suda T, Udagawa N, Takahashi N
  • Journal Title: Proc Natl Acad Sci UAS Volume: (In press)
  • Peer Reviewed
• [Journal Article] Regulatory mechanism of osteoclastogenesis by Wnt signaling
  • Author(s): Kobayashi Y, Maeda K, Uehara S, Yamashita T, Takahashi N
  • Journal Title: Inflammation and Regeneration Volume: (In press)
  • NAID: 130004943807
  • Peer Reviewed
• [Journal Article] c-Fos plays an essential role in the up-regulation of RANK expression in osteoclast precursors within the bone microenvironment
  • 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 Science Volume: (In press)
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22454522
  • Peer Reviewed
• [Journal Article] Bone Effects of vitamin D-Discrepancies between in vivo and in vitro studies-
  • Author(s): Suda T, Takahashi F, Takahashi N
  • Journal Title: Arch Biochem Biophys Volume: (In press)
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22107950
  • Peer Reviewed
• [Presentation] Osteoclast precursors in vivo (2012)
  • Author(s): Naoyuki Takahashi
  • Organizer: 東京医科歯科大学GCOE
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 2012-01-24
• [Presentation] 分子メカニズムを知る意味とは(招待講演) (2011)
  • Author(s): 高橋直之
  • Organizer: Dentistry Quo Vadis
  • Place of Presentation: 東京
  • Year and Date: 2011-12-11
• [Presentation] チタンインプラント埋入における生体側のイベント(招待講演) (2011)
  • Author(s): 高橋直之
  • Organizer: Dentistry Quo Vadis
  • Place of Presentation: 東京
  • Year and Date: 2011-12-10
• [Presentation] 骨吸収を調節する骨芽細胞の新しい役割(招待講演) (2011)
  • Author(s): 高橋直之
  • Organizer: 第26回長崎骨粗鬆症研究会
  • Year and Date: 2011-11-30
• [Presentation] 骨吸収を調節する骨芽細胞の新しい役割 (2011)
  • Author(s): 高橋直之
  • Organizer: 第26回長崎骨粗鬆症研究会
  • Place of Presentation: 長崎県医師会館(長崎)(招待講演)
  • Year and Date: 2011-11-30
• [Presentation] Quiescent Osteoclast Precursors (2011)
  • Author(s): Naoyuki Takahashi
  • Organizer: Invited lecture 2^<nd> Asia-Pacific Osteoporosis and Bone Meeting
  • Year and Date: 2011-09-07
• [Presentation] Quiescent Osteoclast Precursors (2011)
  • Author(s): Naoyuki Takahashi
  • Organizer: 2nd Asia-Pacific Osteoporosis and Bone Meeting
  • Place of Presentation: Gold Coast Convention center Gold Coast, Autraria(招待講演)
  • Year and Date: 2011-09-07
• [Presentation] 破骨細胞を制御する骨芽細胞の新しい役割(招待講演) (2011)
  • Author(s): 高橋直之
  • Organizer: 九州大学大学院講義
  • Place of Presentation: 福岡
  • Year and Date: 2011-05-12
• [Presentation] 骨吸収の調節機構 (2011)
  • Author(s): 高橋直之
  • Organizer: 鹿児島大学歯学部セミナー
  • Year and Date: 2011-01-16
• [Presentation] Noncanonical Wnt signaling and osteoclastogenesis (2010)
  • Author(s): Naoyuki Takahashi
  • Organizer: 22nd Meeting of Korean Society of Bone Metabolism
  • Place of Presentation: Sheraton Grande Walkerhill, 韓国
  • Year and Date: 2010-11-13
• [Presentation] 骨吸収を調節するRANKL-RANK 系 (2010)
  • Author(s): 高橋直之
  • Organizer: 第28回日本骨代謝会学術集会, ランチョンセミナー
  • Place of Presentation: 京王プラザホテル、東京
  • Year and Date: 2010-07-21