Development of alveolar bone turnover control method based on Wnt5a

• Project/Area Number: 25293423
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/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, 教授 (20264252)
• Co-Investigator(Kenkyū-buntansha): 平賀 徹 松本歯科大学, 歯学部, 准教授 (70322170) ; 高橋 直之 松本歯科大学, 総合歯科医学研究所, 教授 (90119222) ; 山下 照仁 松本歯科大学, 総合歯科医学研究所, 准教授 (90302893)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: Wnt5a / 破骨細胞 / 骨芽細胞 / 骨代謝回転

Outline of Final Research Achievements

In order to shorten the treatment period of orthodontic treatment, we tried to elucidate the bone turnover control mechanism by Wnt5a, a cytokine, and to develop a method for controlling alveolar bone turnover based on it. Using genetically modified mice, we analyzed the role of Wnt5a in bone resorption and formation. Wnt5a enhanced the expression of Wnt co-receptor Lrp 5/6 and promoted osteoblast differentiation by β-catenin-dependent Wnt　signaling pathway. Furthermore, Wnt5a suppressed the inhibitory action of Wnt16 in osteoclast differentiation. Osteoclast-derived factors suppressed the expression of sclerostin and promoted bone formation. Thus, these studies suggested that Wnt5a promotes bone turnover in alveolar bone tissues.

Research Products

• [Journal Article] Wnt Signaling Inhibits Osteoclast Differentiation by Activating Canonical and Noncanonical cAMP/PKA Pathways. (2016)
  • Author(s): Weivoda MM, Ruan M, Hachfeld CM, Pederson L, Howe A, Davey RA, Zajac JD, Kobayashi Y, Williams BO, Westendorf JJ, Khosla S, Oursler MJ.
  • Journal Title: J Bone Miner Res. Volume: 31 Issue: 1 Pages: 65-75
  • DOI: 10.1002/jbmr.2599
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Wnt16 regulates osteoclast differentiation in conjunction with Wnt5a. (2015)
  • Author(s): Kobayashi Y, Thirukonda GJ, Nakamura Y, Koide M, Yamashita T, Uehara S, Kato H, Udagawa N, Takahashi N
  • Journal Title: Biochem Biophys Res Commun Volume: 463 Issue: 4 Pages: 1278-1283
  • DOI: 10.1016/j.bbrc.2015.06.102
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The regulation of osteoclast differentiation by Wnt signals. (2015)
  • Author(s): Kobayashi Y, Uehara S, Koide M, Takahashi N
  • Journal Title: Bonekey Rep Volume: 4 Pages: 713-713
  • DOI: 10.1038/bonekey.2015.82
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The regulation of osteoclast differentiation by Wnt signals (2015)
  • Author(s): Kobayashi Y, Uehara S, Koide M, Takahashi N
  • Journal Title: Bonekey Rep Volume: 4 Issue: 4 Pages: 713-713
  • DOI: 10.1093/jb/mvv124
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dnmt3a regulates osteoclast differentiation by coupling to an S-adenosyl methionine-producing metabolic pathway. (2015)
  • Author(s): Nishikawa et al.
  • Journal Title: Nature Medicine Volume: 21 Issue: 3 Pages: 281-287
  • DOI: 10.1038/nm.3774
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Stability of mRNA influences steoporotic bone mass via CNOT3 (2014)
  • Author(s): Watanabe, C. Morita, M. Yamamoto T. (13名)
  • Journal Title: Natl Acad Sci U S A Volume: Vol.111 Issue: 7 Pages: 2692-2697
  • DOI: 10.1073/pnas.1316932111
  • Peer Reviewed / Open Access
• [Journal Article] Arctigenin inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways. (2014)
  • Author(s): Yamashita T, Uehara S, Udagawa N, Li F, Kadota S, Esumi H, Kobayashi Y, Takahashi N
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: 85878-85878
  • DOI: 10.1371/journal.pone.0085878
  • Peer Reviewed / Open Access
• [Journal Article] Noncanonical Wnt5a enhances Wnt/-catenin signaling during osteogenesis. (2014)
  • Author(s): Okamoto, M., Udagawa, N., Yamashita, T., Nakamichi, Y., Uehara, S., Kato, H., Saito, N., Minami, Y., Takahashi, N., Kobayashi, Y.
  • Journal Title: Sci. report Volume: 4 Issue: 1 Pages: 4493-4493
  • DOI: 10.1038/srep04493
  • Peer Reviewed / Open Access
• [Presentation] Wnt5a enhances Wnt/beta-catenin signaling through the up-regulation of Lrp5/6 during osteogenesis (2013)
  • Author(s): Okamoto M, UdagawaN, Yamashita T, Uehara S, Kato H, Saito N, Minami Y, Takahashi N, Kobayashi Y
  • Organizer: 2013 米国骨代謝学会
  • Place of Presentation: Baltimore Convention Center, USA