軟骨内骨化を統合的に制御する分子ネットワークの解明

• 研究課題/領域番号: 18209047
• 研究種目: 基盤研究(A)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 整形外科学
• 研究機関: 東京大学
• 研究代表者: 川口 浩 東京大学, 医学部附属病院, 准教授 (40282660)
• 研究分担者: 鄭 雄一 東京大学, 大学院・工学系研究科, 教授 (30345053) ; 中村 耕三 東京大学, 医学部附属病院, 教授 (60126133) ; 池田 敏之 東京大学, 医学部附属病院, 特任助教 (80322759) ; 齋藤 琢 東京大学, 医学部附属病院, 特任助教 (30456107)
• 研究期間 (年度): 2006 – 2009
• 研究課題ステータス: 完了 (2009年度)
• 配分額: 49,140千円 (直接経費: 37,800千円、間接経費: 11,340千円); 2009年度: 6,890千円 (直接経費: 5,300千円、間接経費: 1,590千円); 2008年度: 8,450千円 (直接経費: 6,500千円、間接経費: 1,950千円); 2007年度: 14,300千円 (直接経費: 11,000千円、間接経費: 3,300千円); 2006年度: 19,500千円 (直接経費: 15,000千円、間接経費: 4,500千円)
• キーワード: 骨 / 軟骨代謝学 / 軟骨代謝 / 転写因子 / p63 / 軟骨細胞 / 軟骨内骨化 / 軟骨

研究概要

軟骨細胞の発生分化に必須である転写因子SOXファミリーのうち、SOX6を強力に誘導する分子として転写因子p63を同定した。本研究ではp63があらゆる分化段階の軟骨細胞に発現し、p63をノックアウトすると四肢の軟骨細胞の発生分化が著しく抑制されること、軟骨の初期分化や軟骨基質産生、増殖、骨組織への置換などあらゆるステップに重要であることなどを、マウスや培養細胞を用いた解析によって明らかにした。

研究成果

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• [雑誌論文] Kruppel-like factor 5 causes cartilage degradation through transactivation of matrix metalloproteinase 9 (2008)
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• [雑誌論文] Patched1 haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity (2008)
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• [雑誌論文] Analysis of the Runx2 promoter in osseous and non-osseos cells and identification of HIF2A as a potent transcriptional activaitor. (2008)
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  • 査読あり
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  • 雑誌名: J Bone Miner Res 21 ページ: 219-227
• [雑誌論文] Carminerin contributes to chondrocyte calcification during endochondral ossification (2006)
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  • 雑誌名: Nature Med 12 ページ: 665-670
• [雑誌論文] Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint after induction of knee joint instability. (2006)
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  • 雑誌名: Arthritis Rheum 54 ページ: 2462-2470
• [雑誌論文] Physiological role of bone morphogenetic proteins in osteogenesis. (2006)
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  • 雑誌名: J Bone Miner Metab. 24 ページ: 95-99
• [雑誌論文] Molecular backgrounds of age-related osteoporosis from mouse genetics approaches. (2006)
  • 著者名/発表者名: Hiroshi Kawaguchi, et al.
  • 雑誌名: Rev Endocr Metab Disord 7 ページ: 17-22
• [雑誌論文] Risk factors for knee osteoarthritis in Japanese men : a case-control study. (2006)
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  • 雑誌名: Mod Rheumatol 16 ページ: 24-29
• [雑誌論文] Cartilage tissue engineering using human auricular chondrocytes embedded in different hydrogel materials. (2006)
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• [雑誌論文] Decreased activities of daily living and associations with bone loss among aged residents in a rural Japanese community : the Miyama Study. (2006)
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• [雑誌論文] Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. (2006)
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• [雑誌論文] Distinct association of gene polymorphisms of estrogen receptor and vitamin D receptor with lumbar spondylosis in postmenopausal women. (2006)
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• [雑誌論文] Grafting of biocompatible polymer for longevity of artificial hip joints. (2006)
  • 著者名/発表者名: Toru Moro, et al.
  • 雑誌名: Clin Orthop Rel Res 453 ページ: 58-63
• [雑誌論文] Tailor-made tricalcium phosphate bone implant directly fabricated by a three-dimensional ink-jet printer. (2006)
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• [雑誌論文] 骨・軟骨再生促進因子 (2006)
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• [雑誌論文] Transcriptional regulation of endochondral ossification by HIF-2α during skeletal growth and osteoarthritis development
  • 著者名/発表者名: Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S, Nishida N, Akune T, Yoshimura N, Nakagawa T, Nakamura K, Tokunaga K, Chung UI, Kawaguchi H.
  • 雑誌名: Nat Med (in press)
• [雑誌論文] GSK-3beta controls osteogenesis through regulating Runx2 activity
  • 著者名/発表者名: Kugimiya F, Kawaguchi H, Ohba S, Kawamura N, Hirata M, Chikuda H, Azuma Y, Woodgett JR, Nakamura K, Chung UI.
• [雑誌論文] Identification and characterization of the human SOX6 promoter.
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• [雑誌論文] Identification of a potent combination of osteogenic genes for bone regeneration using embryonic stem(ES) cell-based sensor.
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• [学会発表] Molecular backgrounds of cartilage degeneration during os teoarthritis progression (Special Lecture : OARSI-KORS Cosponsored Symposium) (2009)
  • 著者名/発表者名: Kawaguchi H
  • 学会等名: The 35^<th> Annual Meeting of the Korean Orthopaedic Research Society
  • 発表場所: Seoul, Korea
  • 年月日: 2009-10-14
• [学会発表] Molecular backgrounds of cartilage degeneration during osteoarthritis progression(Special Lecture : OARSI-KORS Co-sponsored Symposium). (2009)
  • 著者名/発表者名: Hiroshi Kawaguchi
  • 学会等名: The 35^<th> Annual Meeting of the Korean Orthopaedic Research Society
  • 発表場所: Seoul, Korea
  • 年月日: 2009-10-14
• [学会発表] Transcriptional regul ation of osteoarthritis progression (2008)
  • 著者名/発表者名: Kawaguchi H
  • 学会等名: The 13th Congress of the Asia Pacif is League of Associations for Rheuma tology (APLAR 2008)
  • 発表場所: Yokohama
• [学会発表] Transcriptional regulation of osteoarthritis progression (2008)
  • 著者名/発表者名: Hiroshi Kawaguchi
  • 学会等名: The 13th Congress of the Asia Pacific League of Associlations for Rheumatology(APLAR 2008)
  • 発表場所: Yokohama
• [学会発表] p63 Plays a Centr al Role in Cartilage Development by Directly Regulating Key Genes for Ch ondrogenesis (2007)
  • 著者名/発表者名: Ikeda T, et al.
  • 学会等名: ASBMR 29^<th> Annual Meeting
  • 発表場所: Hawaii, USA
  • 年月日: 2007-09-18
• [学会発表] p63 Plays a Central Role in Cartilage Development by Directly Regulating Key Genes for Chondrogenesis (2007)
  • 著者名/発表者名: Toshiyuki Ikeda et.al
  • 学会等名: The American Society for Bone and Mineral Research 29th Annual Meeting
  • 発表場所: Hawaii,USA.
  • 年月日: 2007-09-18
• [学会発表] p63 Plays a Central Role in Cartilage Development by Directly Regulating Key Genes for Chondrogenesis (2007)
  • 著者名/発表者名: Tbshiyuld Ikeda
  • 学会等名: ASBMR 29thAnnual Meeting
  • 発表場所: Hawah,USA
  • 年月日: 2007-09-18
• [学会発表] p63は軟骨の初期分化から後期分化までを統合的に支配するマスター転写因子である (2007)
  • 著者名/発表者名: 池田敏之ら
  • 学会等名: 第25回日本骨代謝学会
  • 発表場所: 大阪
  • 年月日: 2007-07-19
• [図書] OPLL -Ossification of the Posterior Longitudinal Ligament - 2nd Edition(edited by K. Yonenobu, T. Nakamura, Y. Toyama. Springer-Verlag Tokyo) (2006)
  • 著者名/発表者名: Hiroshi Kawaguchi, et al.
  • 総ページ数: 1023
• [図書] OPLL - Ossification of the Posterior Longitudinal Ligament - 2nd Edition" edited by K. Yonenobu, T. Nakamura, and Y. Toyama (2006)
  • 著者名/発表者名: Hiroshi Kawaguchi, et al.
  • 総ページ数: 1023
  • 出版者: Springer-Verlag Tokyo
• [備考]
  • URL: http://www.h.u-tokyo.ac.jp/ortho/
• [備考]
  • URL: http://www.h.u-tokyo.ac.jp/ortho/
• [備考]
  • URL: http://www.h.u-tokyo.ac.jp/ortho/
• [産業財産権] 低摩耗性摺動部材及びそれを用いた人工関節 (2006)
  • 発明者名: 京本政之, 二塚健, 石原一彦, 金野智浩, 中村耕三, 高取吉雄, 川口浩, 茂呂徹, 橋本雅美
  • 権利者名: 同左
  • 出願年月日: 2006-12-15