Molecular mechanisms on differentiation or function of osteoblasts and osteoclasts by the Wnt/LRP signaling pathway

• Project/Area Number: 19390469
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Hokkaido University
• Principal Investigator: TAMURA Masato Hokkaido University, 大学院・歯学研究科, 教授 (30236757)
• Co-Investigator(Kenkyū-buntansha): NASHIMOTO Masayuki 新潟薬科大学, 応用生物学部, 教授 (30228069) ; NEMOTO Eiji 東北大学, 大学院・歯学研究科, 講師 (40292221) ; ISHISAKI Akira 岩手医科大学, 歯学部, 教授 (20356439)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2009: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2007: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
• Keywords: 骨形成 / 骨吸収 / Wntシグナル / 骨芽細胞 / Wnt / BMP / オステオプロテゲリン / miRNA

Research Abstract

In this study, we demonstrated that two cellular signaling pathways of Wnt and bone morphogenetic protein (BMP) control both differentiation and function of osteoblasts and osteoclasts during processes of bone formation and resorption. These Wnt and BMP signaling regulates osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor, which can inhibit the production of osteoclasts. The regulation of OPG expression is mediated through two transcription pathways such as Wnt and BMP that involve the OPG promoter. We also demonstrated that osteoblastic differentiation mediated by certain miRNA expression and BMP-2 down-regulates miR-206 expression at the post-transcriptional level and that BMP-2 could regulate miRNA biogenesis by a novel mechanism.

Research Products

• [Journal Article] Role of the Wnt signaling pathway in bone and tooth (2010)
  • Author(s): Tamura M, Nemoto E, Sato MM, Nakashima A, Shimauchi H
  • Journal Title: Front Biosci E2 Pages: 1405-1413
• [Journal Article] Vascular cell-like potential of undifferentiated ligament fibroblasts to construct vascular cell-specific marker-positive blood vessel structures in a PI3K-activation-dependent manner (2010)
  • Author(s): Ohkubo N, Ishisaki A, Iizuka T, Tamura M, Kitagawa Y
  • Journal Title: J Vasc Res 47(5) Pages: 369-383
  • NAID: 120002400574
• [Journal Article] Role of the Wnt signaling pathway in bone and tooth. (2010)
  • Author(s): Tamura, M
  • Journal Title: Front Biosci (印刷中)
  • Peer Reviewed
• [Journal Article] Bone morphogenetic protein-2 down-regulates miR-206 expression by blocking its maturation process (2009)
  • Author(s): Sato MM, Nashimoto M, Katagiri T, Yawaka Y, Tamura M
  • Journal Title: Biochem Biophys Res Commun 383(1) Pages: 125-9
  • NAID: 120001243503
• [Journal Article] Wnt signaling inhibits cementoblast differentiation and promotes proliferation (2009)
  • Author(s): Nemoto E, Koshikawa Y, Kanaya S, Tsuchiya M, Tamura M, Somerman MJ, Shimauchi H
  • Journal Title: Bone 44(5) Pages: 805-12
• [Journal Article] Enamel matrix derivative neutralized the effect of lipopolysaccharide on osteoprotegerin and receptor activator of nuclear factor kappa B ligand expression of osteoblasts (2009)
  • Author(s): Wada Y, Mizuno M, Tamura M
  • Journal Title: Arch Oral Biol 54(4) Pages: 306-12
• [Journal Article] Multipotency of clonal cells derived from swine periodontal ligament and differential regulation by fibroblast growth factor and bone morphogenetic protein (2009)
  • Author(s): Shirai K, Ishisaki A, Kaku T, Tamura M, Furuichi Y
  • Journal Title: J. Periodontal. Res 44(2) Pages: 238-247
• [Journal Article] Inhibition of vascular endothelial growth factor expression by TRUE gene silencing (2009)
  • Author(s): Elbarbary RA, Takaku H, Tamura M, Nashimoto M
  • Journal Title: Biochem Biophys Res Commun 379(4) Pages: 924-7
• [Journal Article] Bone morphogenetic protein-2 enhances Wnt/β-catenin signaling-induced osteoprotegerin expression (2009)
  • Author(s): Sato MM, Nakashima A, Nashimoto M, Yawaka Y, Tamura M
  • Journal Title: Genes Cells 14(2) Pages: 141-153
  • NAID: 120001442847
• [Journal Article] Effect of dentin phosphoprotein on phosphate-induced apoptosis of odontoblast-like cells (2009)
  • Author(s): Fujisawa R, Mizuno M, Tamura M
  • Journal Title: Cells Tissues Organs 189(1-4) Pages: 60-64
• [Journal Article] Wnt signaling inhibits cementoblast differentiation and Promotes proliferation. (2009)
  • Author(s): Nemoto E
  • Journal Title: Bone 44 Pages: 805-12
  • Peer Reviewed
• [Journal Article] Bone morphogenetic protein-2 down-regulates miR-206expression by blocking its maturation process. (2009)
  • Author(s): Sato M
  • Journal Title: Biochem Biophys Res Commun 38 Pages: 125-129
  • Peer Reviewed
• [Journal Article] Bone morphogenetic protein-2 enhances Wnt / β-catenin signaling-induced osteoprotegerin expression (2009)
  • Author(s): Sato M.
  • Journal Title: Genes Cells 14 Pages: 141-153
  • Peer Reviewed
• [Journal Article] Multipotency of clonal cells derived from swine periodontal ligament and differential regulation by fibroblast growth factor and bone morphozenetic protein (2009)
  • Author(s): Shirai K.
  • Journal Title: J. Periodontal. Res. 44 Pages: 238-247
  • Peer Reviewed
• [Journal Article] Wnt signaling inhibits cementoblast differentiation and promotes proliferation (2009)
  • Author(s): Nemoto E.
  • Journal Title: Bone (印刷中)
  • Peer Reviewed
• [Journal Article] The suppressive effect of enamel matrix derivative on osteocalcin gene expression of osteoblast is neutralized by an antibody against TGF-s (2008)
  • Author(s): Wada Y, Mizuno M, Yamamoto E, Nambu S, Tamura, M
  • Journal Title: Periodont 79(2) Pages: 341-347
• [Journal Article] (2008)
  • Author(s): Sato M
  • Journal Title: Interface Oral Health Science 2007(Springer) Pages: 173-178
• [Journal Article] Establishment of cell lines that exhibit pluripotency from miniature swine periodontal ligaments (2007)
  • Author(s): Ibi M, Ishisaki A, Yamamoto M, Wada S, Kozakai T, Nakashima A, Iida J, Takao S, Izumi Y, Yokoyama A, Tamura M
  • Journal Title: Arch. Oral Biol 52(10) Pages: 1002-1008
  • NAID: 120000970795
• [Journal Article] Gene-silencing by the tRNA maturase tRNase ZL under the direction of small guide RNA (2007)
  • Author(s): Nakashima A, Takaku H, Shibata HS, Negishi Y, Takagi M, Tamura M, Nashimoto M
  • Journal Title: Gene Therapy 14 Pages: 75-85
• [Journal Article] Establishment of cell lines that exhibit pluripotency from miniature swine periodontal ligaments. (2007)
  • Author(s): Ibi M
  • Journal Title: Arch Oral Biol 52 Pages: 1002-1008
  • Peer Reviewed
• [Journal Article] The structure of the flexible arm of Thermotoga maritima tRNase Z differs fromthose of homologous enzymes (2007)
  • Author(s): Ishii R
  • Journal Title: Acta Crystallogr Sect F Struct Biol Cryst Commun 63 Pages: 637-641
  • Peer Reviewed
• [Journal Article] The suppressive effect of enamel matrix derivative on osteocalcin gene expression of osteoblast is neutralized by an antibody against TGF-ss (2007)
  • Author(s): Wada Y
  • Journal Title: J Periodont 79 Pages: 341-347
  • Peer Reviewed
• [Presentation] ヒトBcl-2 mRNAを標的とする裸のRNA heptamerによるアポトーシスの誘導 (2009)
  • Author(s): 高橋昌幸、阿部真由美、中島愛子、野崎忠輔、リアド・エルバリバリ、渡部紀宏、西田浩志、佐野峻子、高久洋暁、成田美和子、高橋益廣、田村正人、梨本正之
  • Organizer: 第11回日本RNA学会年会(第11回RNAミーティング
  • Place of Presentation: 新潟
  • Year and Date: 2009-07-29
• [Presentation] ヒトBc1-2 mRNAを標的とする裸のRNA heptamerによるアポトーシスの誘導 (2009)
  • Author(s): 高橋昌幸
  • Organizer: 第11回日本RNA学会年会
  • Place of Presentation: 新潟市、朱鷺メッセ 新潟コンベンションセンター
  • Year and Date: 2009-07-29
• [Presentation] Wnt signaling inhibits cementoblast differentiation and promotes proliferation (2009)
  • Author(s): Nemoto E, Koshikawa Y, Kanaya S, Tsuchiya M, Tamura M, Somerman MJ, Shimauchi H
  • Organizer: The 3rd International Symposium for Interface Oral Health Science in Sendai
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2009-01-14
• [Presentation] Regulation of miR-206 expression by bone morphogenetic protein-2 through post- transcriptional microRNA maturation in myoblastic C2C12 cells (2009)
  • Author(s): Sato M, Yawaka Y, Tamura M
  • Organizer: The 3rd International Symposium for Interface Oral Health Science in Sendai
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2009-01-14
• [Presentation] BMP-2とWntシグナルによるmiR-206発現調節と細胞分化制御 (2008)
  • Author(s): 佐藤真理, 八若保孝, 田村正人
  • Organizer: 第31回日本分子生物学会、第81回日本生化学会大会合同大会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] Noncanonical Wnt signaling is involved mir-206 expression in osteoblastic differentiation (2008)
  • Author(s): Sato M, Nashimoto M, Kanayama D, Yawaka Y, Tamura M
  • Organizer: 30th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Montreal, Quebec, Canada
  • Year and Date: 2008-09-14
• [Presentation] Identification of a novel Wnt/β-catenin response element in the osteoprotegrin gene promoter and its regulation with bone morphogenetic protein-2 signaling (2008)
  • Author(s): Sato M, Nakashima A, Nashimoto M, Yawaka Y, Tamura M
  • Organizer: The 28th Sapporo Cancer Seminar
  • Place of Presentation: Sapporo
  • Year and Date: 2008-06-26
• [Presentation] Wnt/β-cateninシグナルによって誘導される遺伝子のosteoprotegerin発現調節機構の解析 (2008)
  • Author(s): 佐藤真理, 田村正人, 八若保孝
  • Organizer: 第46回日本小児歯科学会大会
  • Place of Presentation: 大宮
  • Year and Date: 2008-06-12
• [Presentation] Wnt/β-cateninとBMP-2シグナルによるosteo protegerin遺伝子の発現調節 (2008)
  • Author(s): 佐藤真理, 八若保孝, 田村正人
  • Organizer: 日本分子生物学会第8回春季シンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 2008-05-26
• [Presentation] Wnt/β-cateninとBMP-2シグナルによるosteoprotegerin遺伝子の発現調節 (2008)
  • Author(s): 佐藤真理
  • Organizer: 日本分子生物学会第8回春季シンポジウム
  • Place of Presentation: 京王プラザホテル札幌
  • Year and Date: 2008-05-26
• [Presentation] Wnt/beta-catenin inhibits cementoblast differentiation in vitro (2008)
  • Author(s): Nemoto E, Koshikawa Y, Kanaya S, Tsuchiya M, Tamura M, Somerman M. Shimauchi H
  • Organizer: 86th General Session & Exhibition of the IADR Toronto
  • Place of Presentation: Canada
• [Presentation] Wnt/β-cateninシグナルによって誘導されるosteoprotegerin遺伝子の発現調節機構の解析 (2007)
  • Author(s): 佐藤真理, 八若保孝, 田村正人
  • Organizer: 第30回日本分子生物学会・第80回日本生化学会大会合同大会(BMB200 7)
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-19
• [Presentation] Identification of a novel Wnt/β-catenin response element in the osteoprotegrin gene promoter and its re gulation with bone morphogenetic protein-2 signaling (2007)
  • Author(s): Sato M, Nakashima A, Nashimoto M, Yawaka Y, Tamura M
  • Organizer: 29th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Honolulu, HI, USA
  • Year and Date: 2007-09-16
• [Presentation] Identification of a Novel Wnt/β-Catenin Response Element in the Osteoprotegrin Gene Promoter and its Regulation with Bone Morphogenetic Protein-2 Signaling. (2007)
  • Author(s): Sato M
  • Organizer: 29th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Hawaii Convention Center Honolulu, HI, USA
  • Year and Date: 2007-09-16
• [Presentation] Wnt/β-cateninとBMP-2シグナルによるOPG遺伝子の発現調節機構の解析 (2007)
  • Author(s): 佐藤真理, 田村正人
  • Organizer: 第25回日本骨代謝学会学術大会
  • Place of Presentation: 大阪
  • Year and Date: 2007-07-19
• [Presentation] Wnt/β-cateninとBMP-2シグナルによるOPG遺伝子の発現調節機構の解析 (2007)
  • Author(s): 佐藤真理
  • Organizer: 第25回日本骨代謝学会学術大会
  • Place of Presentation: 大阪国際会議場
• [Presentation] Wnt/β-catenin シグナルによって誘導される osteoprotegerin 遺伝子の発現調節機構の解析 (2007)
  • Author(s): 佐藤真理
  • Organizer: 第30回日本分子生物学会、第80回日本生化学会大会合同大会
  • Place of Presentation: パシフィコ横浜
• [Book] Regulation of microRNA expression by bone morphogene tic protein-2(T. Sasano, O. Suzuki (Eds.)) (2010)
  • Author(s): Sato M, Yawaka Y, Tamura M
  • Publisher: Springer
• [Book] Wnt/beta-catenin inhibits cementoblast differentiation(T. Sasano, O. Suzuki (Eds.)) (2010)
  • Author(s): Nemoto E, Koshikawa Y, Kanaya S, Tsuchiya M, Tamura M, Somerman M. Shimauchi H
  • Publisher: Springer
• [Book] Regulation of osteoprotegerin and RANKL gene expre ssion by Wnt/β-catenin and bone morpho genetic protein-2 in C2C12 cells(M. Watanabe, O. Okuno (Eds.)) (2007)
  • Author(s): Sato M, Nakashima A, Nashimoto M, Yawaka Y, Tamura M
  • Publisher: Springer