Osteoclast-derived factors for inhibiting sclerostin expression is a bone coupling factor.

• Project/Area Number: 25670792
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional basic 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): KOIDE Masanori 松本歯科大学, 総合歯科医学研究所, 講師 (10367617)
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: スクレロスチン / 破骨細胞 / 骨代謝共役 / 骨代謝 / 骨リモデリング / Wnt / Sost

Outline of Final Research Achievements

Bone remodeling is achieved by the cooperation of bone forming osteoblasts, bone resorbing osteoclasts, and matrix-embedded osteocytes. Sclerostin (Sost) secreted from osteocytes inhibits the Wnt / β- catenin signaling, which in turn, suppresses bone formation. OPG-deficient mice (OPG-KO) exhibit increased bone resorption and formation activity. We have found that the expression of Sost is significantly reduced in OPG-KO mice. This finding suggests that the expression of Sost is regulated by factors associated with the increased bone resorption. We also found that culture supernatant collected from osteoclast cultures suppressed the expression of Sost in UMR106 cells. Thus, this study revealed that osteoclasts secrete cytokines X and then suppress the expression of Sost.

Research Products

• [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] 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 Pages: 1278-1283
  • Peer Reviewed
• [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] 骨細胞による骨吸収制御 (2014)
  • Author(s): 小出雅則
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 大阪国際会議場
  • Invited