骨格形成を司る転写因子ネットワークの解析

2007 Fiscal Year Annual Research Report

• Project/Area Number: 17390493
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: 中島 和久 Tokyo Medical and Dental University, 難治疾患研究所, COE拠点形成特任教員 (90252692)
• Keywords: Osterix / 骨芽細胞 / 破骨細胞 / 骨格 / パターニング / Schnurri-2

Research Abstract

骨格形成を司る転写ネットワークとして、その下流の遺伝子は骨の形成に関わり特に骨芽細胞におけるその機能が明らかであることから、Runx2ならびにOsxとともに主要な機能を担うと推察される。この骨格形成における分子のネットワークの一部として、PlexinD1の意義を検討しその欠失によって骨格のパターニングの異常が起こることを見出した。この異常では、肋骨の形態異常や脊椎椎体の欠失変異更に椎体の軟骨の血管侵入の異常が観察され、本分子の骨格形成における意義が明らかとなった。更にOsxの制御分子の上流にあるBMPの機能についての解析を進め、BMPのターゲットを同時に修飾する分子としてSchnurri-2の意義を検索した。ノックアウトマウスによるこの検索によりSchnurri-2の欠失は、皮質骨ならびに海綿骨のいずれにおいても量の減少をもたらし、その遺伝子発現の検索からOsterixのレベルの低下が明らかとなった。骨の形成の全般的な低下は骨形成速度、骨芽細胞表面更には石灰化速度のいずれにおいても抑制として観察された。一方、破骨細胞の機能に対する抑制がノックアウトにおいて見られ、その抑制のレベルが骨芽細胞の抑制を上回ることから、海綿骨における骨量は増加することが観察された。以上の如く、骨格形成に関わる分子群の意義を明らかにし、またこれの一つの要因としてのOsterixの動きを解明した。

Research Products

• [Journal Article] JunD suppresses bone formation and contributes to low bone mass induced by estrogen depletion. (2008)
  • Author(s): Kawamata A., Izu Y., Yokoyama H., Hayata T., Amagasa T., Wagner E.F., Nakashima K., Ezura Y., Noda M.
  • Journal Title: Journal of Cellular Biochemistry. 103 Pages: 1037-1045
  • Peer Reviewed
• [Journal Article] Transient Receptor Potential Vanilloid 4 Deficiency Suppresses Unloading-Induced Bone Loss. (2008)
  • Author(s): Mizoguchi F., Mizuno A., Hayata T., Nakashima K., Heller S., Ushida T., Sokabe M., Miyasaka N., Suzuki M., Ezura Y., Noda M.
  • Journal Title: Journal of Cellular Physiology. 216 Pages: 47-53
  • Peer Reviewed
• [Journal Article] OPN deficiency suppresses appearance of odontoclastic cells and resorption of-the tooth root induced by experimental force application (2008)
  • Author(s): Chung C.J., Soma K., Rittling S.R., Denhardt D.T., Hayata T., Nakashima K., Ezura Y., Noda M.
  • Journal Title: Journal of Cellular Physiology 214 Pages: 614-20
  • Peer Reviewed
• [Journal Article] Osteopontin Negatively Regulates parathyroid hormone receptor signaling in osteoblasts (2008)
  • Author(s): Ono N, Nakashima K, Rittling S.R., Schipani E., Hayata T, Ezura Y., Soma K., Denhardt D.T., Kronenberg H.M., Noda M.
  • Journal Title: Journal of Biological Chemistry (In press)
  • Peer Reviewed
• [Journal Article] Lack of schnurri-2 expression associates with reduced bone remodeling and osteonenia. (2007)
  • Author(s): Saita Y., Takagi T., Kitahara K., Usui M., Ezura Y., Nakashima_K., Kurosawa H., Ishii S., Noda M.
  • Journal Title: Journal of Biological Chemistry 282 Pages: 12907-15
  • Peer Reviewed
• [Journal Article] Constitutively active parathyroid hormone receptor signaling in cells in osteoblastic lineage suppresses mechanical unloading-induced bone resorution. (2007)
  • Author(s): Ono N., Nakashima K., Schipani E., Hayata T., Ezura Y., Soma K., Kronenberg H. M., Noda M.
  • Journal Title: Journal of Biological Chemistry 282 Pages: 25509-16
  • Peer Reviewed
• [Journal Article] PlexinD1 deficiency induces defects in axial skeletal morphogenesis. (2007)
  • Author(s): Kanda T., Yoshida Y., Izu Y., Nifuji A., Ezura Y., Nakashima K., Noda M.
  • Journal Title: Journal of Cellular Biochemistry 101 Pages: 1329-1337
  • Peer Reviewed
• [Journal Article] Osteopontin deficiency enhances anabolic action of EP4 agonist at a sub-optimal dose in bone. (2007)
  • Author(s): Kato N., Kitahara K., Rittling S.R., Nakashima K., Denhardt D.T., Kurosawa H., Ezura Y., Noda M.
  • Journal Title: Journal of Endocrinology. 101 Pages: 979-86
  • Peer Reviewed
• [Journal Article] Serum osteopontin, an enhancer of tumor metastasis to bone, promotes B16 melanoma cell migration. (2007)
  • Author(s): Hayashi C., Rittling S., Hayata T., Amagasa T., Denhardt_D. T., Ezura Y., Nakashima K., Noda M.
  • Journal Title: Journal of Cellular Biochemistry. 101 Pages: 979-86
  • Peer Reviewed
• [Journal Article] Cnot7 Null Mice Exhibit High Bone Mass Phenotype and Modulation of BMP Actions. (2007)
  • Author(s): Washio-Oikawa K., Nakamura T., Usui M., Yoneda M., Ezura Y., Ishikawa I., Nakashima K, Noda T., Yamamoto T., Noda M.
  • Journal Title: Journal of Bone Mineral Research 22 Pages: 1217-23
  • Peer Reviewed
• [Journal Article] Nanogel-based delivery system enhances PGE(2)effects on bone formation. (2007)
  • Author(s): Kato N., Hasegawa U., Morimoto N., Saita Y., Nakashima K., Ezura Y., Kurosawa H., Akiyoshi K., Noda M.
  • Journal Title: Journal of Cellular Biochemistry 101 Pages: 1063-70
  • Peer Reviewed
• [Presentation] 機械的負荷の除去による骨吸収は骨芽細胞特異的な副甲状腺ホルモン受容体シグナルの活性化により抑制される (2007)
  • Author(s): 小野 法明、相馬 邦道、中島 和久、野田 政樹
  • Organizer: 第66回日本矯正歯科学会大会
  • Place of Presentation: 大阪
  • Year and Date: 20070920-21
• [Presentation] Angiotensin II suppresses bone mass via AT1 receptor in Long Bones of Adult Mice (2007)
  • Author(s): Izu Y., Hayata T., Hemmi H., Nagata J., Ezura Y., Nakashima K., Noda M.
  • Organizer: The 29th Annual Meeting of American Society for Bone-and Mineral Research
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 20070916-19
• [Presentation] Osteoclast Specific Ablation of Dicer Suppresses Bone Resorption and Increases Bone Mass (2007)
  • Author(s): Mizoguchi F., Nakamura T., Hayata T., Hemmi H., Ezura Y., Nakashima K., Miyasaka N., Harfe B., Kato S., Noda M.
  • Organizer: The 29th Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 20070916-19
• [Presentation] Dok-1 and Dok-2 Deficiency Enhances Bone Resorption and Modulates the Geometry of Bone In Vivo (2007)
  • Author(s): Kawamata A., Inoue A., Ezura Y., Nakashima K., Amagasa T, Yamanashi Y., Noda M.
  • Organizer: The 29th Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 20070916-19
• [Presentation] Responses of Bone in ANA Knock-out Mice to Ovariectomy (2007)
  • Author(s): Miyai K., Yoneda M., Mizoguchi F., Hayata T., Ezura Y., Nakashima K., Yamamoto T., Noda M.
  • Organizer: The 29th Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 20070916-19
• [Presentation] β-adrenergic Signaling Requires Bone Matrix Protein OPN to Suppress Bone Formation and to Activate Bone Resorption (2007)
  • Author(s): Nagao M., Saita Y., Nagata J., Izu Y., Hayata T., Hemmi H., Ezura Y., Nakashima K., Kurosawa H., Noda M.
  • Organizer: The 29th Annual Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 20070916-19
• [Presentation] β2 Adrenergic Receptor Deficiency Enhances Bone Mass in by Antagonizing Against Aging-induced Bone Loss and Blunts Anabolic Effects of PTH on Osteoblasts (2007)
  • Author(s): Hanyu R., Saita Y., Nagata J., Izu Y., Hayata T., Hemmi H., Takeda S., Ezura Y., Nakashima K., Kurosawa H., Noda M.
  • Organizer: The 29th Annual-Meeting of American Society for Bone and Mineral Research
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 20070916-19
• [Presentation] TRPV4 is a mechanosensitive channel that mediates unloading-induced supression of bone formation and activation of bone resorption. (2007)
  • Author(s): Mizoguchi F., Mizuno A., Ezura Y., Nakashima K., Miyasaka N., Suzuki M., Noda M.
  • Organizer: The 17th Scientific Meeting International Bone & Mineral Society
  • Place of Presentation: Montreal, Canada
  • Year and Date: 20070624-29