Link between estrogen and TGF-beta signaling in intervertebral disc metabolism - possible therapeutic target for degenerative disc disease

• Project/Area Number: 19591734
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Keio University
• Principal Investigator: CHIBA Kazuhiro Keio University, 医学部, 准教授 (80179952)
• Co-Investigator(Kenkyū-buntansha): TAKAISHI Hironari 慶應義塾大学, 医学部, 助教 (60236180) ; TSUJI Takashi 慶應義塾大学, 医学部, 助教 (60296639)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: エストロゲン / 椎間板 / 軟骨 / 2型コラーゲン / TGF-β / MAPK / 腰痛 / 椎間板変性 / 骨粗鬆症 / Smad

Research Abstract

軟骨細胞において、エストロゲンはエストロゲン受容体α(ERα)依存性にTGF-β下流のp38MAPキナーゼシグナルと相乗的に作用することで、II型コラーゲン遺伝子発現を誘導することが明らかになった。卵巣摘出モデルおよびERα欠損マウスの表現型から、リガンド結合型ERαは椎体軟骨終板および椎間板基質の恒常性維持に寄与していることが示唆された。

Research Products

• [Journal Article] Novel apatite fiber scaffolds can promote three-dimensional proliferation of osteoblasts in rodent bone regeneration models (2009)
  • Author(s): Morisue H, Matsumoto M, Chiba K, Matsumoto H, Toyama Y, Aizawa M, Kanzawa N, Fujimi TJ, Uchida H, Okada I
  • Journal Title: J Biomed Mater Res A. Epub ahead of print
  • Peer Reviewed
• [Journal Article] Novel apatite fiber scaffolds can promote three-dimensional proliferation of osteoblasts in rodent bone regeneration models. (2009)
  • Author(s): Morisue H, Matsumoto M, Chiba K, Matsumoto H, Toyama Y, Aizawa M, Kanzawa N, Fujimi TJ, Uchida H, Okada I.
  • Journal Title: J Biomed Mater Res A. (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor-A is a survival for nucleus pulposus cells in the intervertebral disc (2008)
  • Author(s): Fujita N, Chiba K
  • Journal Title: Biochem Biophys Res Commun 372巻 Pages: 367-372
  • Peer Reviewed
• [Journal Article] A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation (2008)
  • Author(s): Hirose Y, Chiba K
  • Journal Title: Am J Hum Genet 82巻 Pages: 1122-1129
  • Peer Reviewed
• [Journal Article] Japanese Orthopaedic Association Back Pain Evaluation Questionnaire. Part 3. Validity study and establishment of the measurement scale : Subcommittee on Low Back Pain and Cervical Myelopathy Evaluation of the Clinical Outcome Committee of the Japanese Orthopaedic Association, Japan (2008)
  • Author(s): Fukui M, Chiba K
  • Journal Title: J Orthop Sci 13巻 Pages: 173-179
  • Peer Reviewed
• [Journal Article] Surgical results and related factors for ossification of posterior longitudinal ligament of the thoratic spine : a multi-institutional retrospective study (2008)
  • Author(s): Matsumoto M, Chiba K
  • Journal Title: Spine 33巻 Pages: 1034-1041
  • Peer Reviewed
• [Journal Article] Risk factors for closure of lamina after open-door laminoplasty (2008)
  • Author(s): Matsumoto M, Chiba K
  • Journal Title: J Neurosurg Spine 9巻 Pages: 530-537
  • Peer Reviewed
• [Journal Article] A compound heterozygote of novel and recurrent DTDST mutations results in a novel intermediate phenotype of Desbuquois dysplasia, diastrophic dysplasia, and recessive form of multiple epiphyseal dysplasia (2008)
  • Author(s): Miyake A, Nishimura G, Futami T, Ohashi H, Chiba K, Toyama Y, Furuichi T, Ikegawa S
  • Journal Title: J Hum Genet Pages: 367-372
  • NAID: 10021929219
  • Peer Reviewed
• [Journal Article] Surgical treatment of intramedullary spinal cord tumors : prognosis and complications (2008)
  • Author(s): Nakamura M, Ishii K, Watanabe K, Tsuji T, Takaishi H, Matsumoto M, Toyama Y, Chiba K
  • Journal Title: Spinal Cord 46巻 Pages: 282-286
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor-A is a survival for nucleus pulposus cells in the intervertebral disc. (2008)
  • Author(s): Fujita N, Chiba K
  • Journal Title: Biochem Biophys Res Commun 372 Pages: 367-372
  • Peer Reviewed
• [Journal Article] A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation. (2008)
  • Author(s): Hirose Y, Chiba K
  • Journal Title: Am J Hum Genet 82 Pages: 1122-1129
  • Peer Reviewed
• [Journal Article] Japanese Orthopaedic Association Back Pain Evaluation Questionnaire. Part 3. Validity study and establishment of the measurement scale : Subcommittee on Low Back Pain and Cervical Myelopathy Evaluation of the Clinical Outcome Committee of the Japanese Orthopaedic Association, Japan. (2008)
  • Author(s): Fukui M, Chiba K
  • Journal Title: J Orthop Sci 13 Pages: 173-179
  • Peer Reviewed
• [Journal Article] Surgical results and related factors for ossification of posterior longitudinal ligament of the thoratic spine : a multi-institutional retros pective study. (2008)
  • Author(s): Matsumoto M, Chiba K
  • Journal Title: Spine 33 Pages: 1034-1041
  • Peer Reviewed
• [Journal Article] Risk factors for closure of lamina after open-door laminoplasty. (2008)
  • Author(s): Matsumoto M, Chiba K
  • Journal Title: J Neurosurg Spine 9 Pages: 530-537
  • Peer Reviewed
• [Journal Article] A compound heterozygote of novel and recurrent DTDST mutations results in a novel intermediate phenotvpe of Desbuquois dysplasia, diastrophic dysplasia, and recessive form of multiple epiphyseal dysplasia. (2008)
  • Author(s): Miyake A, Nishimura G, Futami T, Ohashi H, Chiba K, Toyama Y, Furuichi T, Ikegawa s.
  • Journal Title: J Hum Genet Pages: 367-372
  • Peer Reviewed
• [Journal Article] Surgical treatment of intramedullary spinal cord tumors : prognosis and complications. (2008)
  • Author(s): Nakamura M, Ishii K, Watanabe K, Tsuji T, Takaishi H, Matsumoto M, Toyama Y, Chiba K.
  • Journal Title: Spinal Cord. 46 Pages: 282-286
  • Peer Reviewed
• [Presentation] A Possible Link between Estrogen and TGF-β Signaling in Intervertebral Disc Metabolism : Estrogen receptor α-Dependent Regulation of Type II Collagen Gene Expression in Chondrocytic Cells (2009)
  • Author(s): 加藤雅敬, 高石官成, 千葉一裕
  • Organizer: 55^<th> Annual Meeting of Orthopaedic Researh Society
  • Place of Presentation: アメリカ(ラスベガス)
  • Year and Date: 2009-02-22
• [Presentation] A possible link betwee n estrogen and TGF-β signaling in intervert ebral disc metabolism : Estrogen receptor-alp ha-dependent regulation of type II collagen gene expression in chondrocytic cells (2009)
  • Author(s): Kato, M., et al.
  • Organizer: 55^<th> Annual Meeting of Orthopaedic Researh Society
  • Place of Presentation: Sands Expo Convention Center NV USA
• [Presentation] 卵巣摘出ラットにおける椎間板変性機序の解析(第2報)ERαを介したII型コラーゲン遺伝子の転写制御について (2008)
  • Author(s): 加藤雅敬(KATO MASANORI)
  • Organizer: 第23回日本整形外科学会基礎学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-10-24
• [Presentation] 卵巣摘出ラットにおける椎間板変性機序の解析-第2報 : ERαを介しかII型コラーゲン遺伝子の転写制御について- (2008)
  • Author(s): 加藤雅敬, 高石官成, 千葉一裕
  • Organizer: 第23回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-24
• [Presentation] Estorgen Regulates Type II Collagen Gene Expression via ERalpha-dependent Genomic Actions in Rat Intervertebral Disc Cells (2008)
  • Author(s): Kato, M., et al.
  • Organizer: 第23回日本整形外科学会基礎学術集会2008年国際腰椎学会
  • Place of Presentation: Geneva Switzerland
  • Year and Date: 2008-05-26
• [Presentation] Estorgen Regulates Type II Collagen Gene Expression via ERalpha-dependent Genomic Actions in Rat Intervertebral Disc Cells (2008)
  • Author(s): 加藤雅敬, 高石官成, 千葉一裕
  • Organizer: 第35回国際腰椎学会
  • Place of Presentation: ジュネーブ
  • Year and Date: 2008-05-26
• [Presentation] Type II Collagen Gene Expression of Intervertebral Disc in Ovariectomized Rats. (2008)
  • Author(s): M. Kato, H. Takaishi, K. Chiba
  • Organizer: 54^Annual Meeting of Orthopaedic Researh Society.
  • Place of Presentation: San Francisco,CA
  • Year and Date: 2008-03-03
• [Presentation] Type II Collagen Gene Expression of Intervertebral Disc in Ovariecto mized Rats (2008)
  • Author(s): Kato, M., et al.
  • Organizer: 54^<th> Annual Meeting of Orthopaedic Researh Soci ety
  • Place of Presentation: San Francisco, CA USA
• [Presentation] ラット卵巣摘出モデルにおいて椎間板変性経時的に進行する (2007)
  • Author(s): 加藤 雅敬, 高石 官成, 千葉 一裕
  • Organizer: 第22回日本整形外科学会に基礎学術集会
  • Place of Presentation: 浜松
  • Year and Date: 2007-10-26
• [Presentation] Type II Collagen Gene Expression of Intervertebral Disc in Ovariectomized Rats. (2007)
  • Author(s): M. Kato, H. Takaishi, K. Chiba
  • Organizer: 6^Combined Meeting of Orthopaedic Research Society.
  • Place of Presentation: Honolulu,HI
  • Year and Date: 2007-10-23
• [Presentation] Degeneration of Intervertebral Disc in Ovariectomized Rats. (2007)
  • Author(s): M. Kato, H. Takaishi, K. Chiba
  • Organizer: 29^The American Society for Bone and Mineral Research.
  • Place of Presentation: Honolulu,HI
  • Year and Date: 2007-09-18
• [Presentation] Degeneration of Inte rvertebral Disc in Ovariectomized Rats (2007)
  • Author(s): Kato, M. et al.
  • Organizer: 29^<th> The American Society for Bone and Mineral Research
  • Place of Presentation: Hawaii Convention Center, HI USA
  • Year and Date: 2007-09-17
• [Presentation] ラット卵巣摘出モデルにおいて椎間板変性は経時的に進行する (2007)
  • Author(s): 加藤雅敬(KATO MASANORI)
  • Organizer: 第25回日本骨代謝学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2007-07-21
• [Presentation] ラット卵巣摘出モデルにおいて椎間板変性は経時的に進行する (2007)
  • Author(s): 加藤 雅敬, 高石 官成, 千葉 一裕
  • Organizer: 第25回日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2007-07-20
• [Presentation] Type II Collagen Gene Expression of Intervertebral Disc in Ovariectomi zed Rats (2007)
  • Author(s): Kato, M., et al.
  • Organizer: 6^<th> Combined Meeting of Orthopaedic Research Society
  • Place of Presentation: Hawaii Convention Center, HI USA