Hematopoietic cells regulate bone metabolism

• Project/Area Number: 23659972
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• 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): MIZOGUCHI Toshihide 松本歯科大学, 総合歯科医学研究所, 講師 (90329475)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 歯科矯正学 / 破骨細胞 / Wnt / 関節炎 / 脂肪細胞 / 骨髄 / Wnt5a / Sfrp5

Research Abstract

Adipose tissues in bone marrow are increased with aging. We therefore explored effects of adipose tissues in bone marrow on bone formation and resorption. The expressionof Wnt5a, which promotes osteoclast formation, was increased in arthritis model mice.The expression of Sfrp5, an inhibitor of Wnt5a, was decreased. Treatment with Sfrp5 inhibited the stimulatory effect of Wnt5a on osteoclast formation. Adipose tissues highly expressed Sfrp5. Enforced expression of Sfrp5 in arthritis mice abrogated bone destruction associated with arthritis.

Research Products

• [Journal Article] Osteoprotegerin-deficient male mice as a model for severe alveolar bone loss: Comparison with RANKL-overexpressing transgenic male mice. (2013)
  • Author(s): Koide M et al.
  • Journal Title: Endocrinology Volume: 190 Issue: 2 Pages: 773-782
  • DOI: 10.1210/en.2012-1928
  • Peer Reviewed / Open Access
• [Journal Article] Roles of Wnt signals in bone resorption during physiological and pathological states. (2013)
  • Author(s): Maeda K et al.
  • Journal Title: J Mol Med (Berl) Volume: 91 Issue: 1 Pages: 15-23
  • DOI: 10.1007/s00109-012-0974-0
  • Peer Reviewed / Open Access
• [Journal Article] Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice. (2012)
  • Author(s): Nakamichi Y et al.
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Issue: 25 Pages: 10006-10011
  • DOI: 10.1073/pnas.1207361109
  • Peer Reviewed
• [Journal Article] c-Fos plays an essential role in theup-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 Volume: 125 Pages: 2910-2917
  • 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 osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis. (2012)
  • Author(s): Maeda K, Kobayashi Y (2), Mizoguchi T (6).
  • Journal Title: Nat Med Volume: 18 Pages: 405-412
  • 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 D analog, increases bone mineral density by suppressing RANKL expression in mouse trabecular bone. (2012)
  • Author(s): Harada S, Mizoguchi T, Kobayashi Y, Nakamichi Y, Takeda S, Sakai 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] Wnt による骨代謝制御機構 (2012)
  • Author(s): 小林泰浩
  • Journal Title: TheBone Volume: 26 Pages: 151-159
• [Journal Article] 骨芽細胞 系細胞と破骨細胞前駆細胞の間の Wnt5a-Ror2 シグナルは破骨細胞形成を亢進す る (2012)
  • Author(s): 小林泰浩,前田和洋、高橋直之
  • Journal Title: 実験医学 Volume: 30 Pages: 1933-1936
• [Journal Article] Wnt シグナルによる骨代謝制御 (2012)
  • Author(s): 小林泰浩、上原俊介
  • Journal Title: 日本抗加齢医学会雑誌 Volume: 8 Pages: 719-725
• [Journal Article] Wnt5a-Ror2 シグナルを標的に した新規骨吸収阻害薬の開発 (2012)
  • Author(s): 小林泰浩
  • Journal Title: ケミカルエンジニアリング Volume: 57 Pages: 921-925
• [Journal Article] Wnt シグナルによる骨代謝制御機構 (2012)
  • Author(s): 小林泰浩
  • Journal Title: Clinical Calcium. Volume: 22 Pages: 1701-1706
• [Journal Article] Roles of Wnt signals in bone resorption during physiological and pathological states. (2012)
  • Author(s): Maeda K
  • Journal Title: Journal of Molecular Medicine Volume: 91 Pages: 15-23
  • 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] 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
• [Presentation] Roles Wnt5a-Ror2 signals in bone resorption (2012)
  • Author(s): Kobayashi Yasuhiro
  • Organizer: 2012年韓国骨代謝学会
  • Place of Presentation: san Medical Center (ソウル、韓国)
  • Year and Date: 2012-11-16
• [Presentation] Wnt5a-Ror2 シグナルのよる破骨細胞分化制御機構 (2012)
  • Author(s): 小林泰浩
  • Organizer: 奥羽大学 歯学部
  • Place of Presentation: 郡山
  • Year and Date: 2012-09-14
• [Presentation] Wnt5a-Ror2 シグナルのよる破 骨細胞の分化と機能の制御機構 (2012)
  • Author(s): 小林泰浩
  • Organizer: 東北大 学大学院セミナー
  • Place of Presentation: 東北大学歯学部(仙台)
  • Year and Date: 2012-09-13
• [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(招待講演)
  • Place of Presentation: 大阪大学歯学部（吹田市）
• [Presentation] Wnt5a-Ror2 シグナルによる破骨細胞の分化と機能の制御機構
  • Author(s): 小林 泰浩
  • Organizer: 東北大学大学院セミナー
  • Place of Presentation: 東北大学歯学部（仙台）
  • Invited
• [Presentation] Wnt5a-Ror2シグナルによる破骨細胞分化制御機構
  • Author(s): 小林 泰浩
  • Organizer: 第54回歯科基礎医学会学術集会「サテライトシンポジウム６」
  • Place of Presentation: 奥羽大学歯学部（郡山）
  • Invited
• [Presentation] Roles of Wnt5a-Ror2 signals in bone resorption.
  • Author(s): Kobayashi Yasuhiro
  • Organizer: 2012 韓国骨代謝学会学術集会
  • Place of Presentation: Asan Medical Center (ソウル, 韓国）
  • Invited