Regulation of chondrogenic differentiation of synovial fibroblasts by BMP signaling and the effect of proinflammtory cytokines

• Project/Area Number: 18591653
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: NAKAYAMA Shuichi The University of Tokyo, 医学部・附属病院, 助教 (80401066)
• Co-Investigator(Kenkyū-buntansha): TANAKA Sakae 東京大学, 医学部・附属病院, 准教授 (50282661) ; KADONO Yuho 東京大学, 医学部・附属病院, 助教 (70401065)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,090,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥690,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: 滑膜線維芽細胞 / bone morphogenetic protein / tumoro necrosis factor-α / p38 MAP キナーゼ / p38 MAPキナーゼ / BMP2 / TNF-alpha / p38 / Smad1 / 5 / 8

Research Abstract

関節リウマチ患者の滑膜線維芽細胞はBMP-2刺激、あるいはALK3CA遺伝子の導入によって軟骨細胞特異的マーカーを発現するようになる。炎症性サイトカインであるTNF-αは勝膜線維芽細胞の軟骨細胞分化を強力に抑制する。この抑制効果の一部はp38MAP キナーゼを介していると考えられた。

Research Products

• [Journal Article] Intraoperative 3-dimensional imaging-based navigation-assisted anatomic double-bundle anterior cruciate ligament reconstruction (2008)
  • Author(s): Nakagawa T, Takeda H, Nakajima K, Nakayama S, Fukai A, Kachi Y, Kawano H, Miura T, Nakamura K
  • Journal Title: Arthroscopy 24 Pages: 1161-1167
• [Journal Article] Tumor necrosis factor-alpha inhibits chondrogenic differentiation of synovial fibroblasts through p38 mitogen activating protein kinase pathways (2008)
  • Author(s): Okuma-Yoshioka C, Seto H, Kadono Y, Hikita A, Oshima Y, Kurosawa H, Nakamura K, Tanaka S
  • Journal Title: Mod Rheumatol 18(4) Pages: 366-378
• [Journal Article] Pivotal role of Bcl-2 family proteins in the regulation of chondrocyte apoptosis (2008)
  • Author(s): Oshima Y, Akiyama T, Hikita A, Iwasawa M, Nagase Y, Nakamura M, Wakeyama H, Kawamura N, Ikeda T, Chung UI, Hennighausen L, Kawaguchi H, Nakamura K, Tanaka S
  • Journal Title: J Biol Chem. 283(39) Pages: 26499-26508
• [Journal Article] RA における破骨細胞分化と関節破壊-RANKL dependent- (2008)
  • Author(s): 田中栄
  • Journal Title: Rheumatology Clinical Update 15 Pages: 15-17
• [Journal Article] 骨研究のフロンテイア (2008)
  • Author(s): 田中栄
  • Journal Title: 炎症・免疫と破骨細胞内分泌・糖尿病科 27 Pages: 249-252
• [Journal Article] 次世代の生物学的製剤 (2008)
  • Author(s): 田中栄
  • Journal Title: デノスマブ分子リウマチ治療 1 Pages: 130-133
• [Journal Article] 骨研究の最前線 (2008)
  • Author(s): 田中栄
  • Journal Title: 破骨細胞のアポトーシスと機能制御最新医学 63 Pages: 2182-2186
• [Journal Article] 目でみる診療基本手技 (2008)
  • Author(s): 田中 栄、廣瀬 旬
  • Journal Title: 診療手技穿刺および生検法関節腔穿刺法Medicina(0025-7699) 45巻13号 Pages: 135-138
• [Journal Article] Tumor necrosis factor-alpha inhibits chondrogenic differentiation of synovial fibroblasts through p38 mitogen activating protein kinase pathways. (2008)
  • Author(s): Okuma-Yoshioka C, Tanaka S, et al.
  • Journal Title: Modern Rheumatology 18(4) Pages: 366-378
  • Peer Reviewed
• [Journal Article] 骨吸収を標的にした関節リウマチ治療戦略 (2007)
  • Author(s): 松本卓巳, 田中栄
  • Journal Title: リウマチ科(0915-227X)(東京大学 医学部整形外科) 41巻1号 Pages: 127-133
• [Journal Article] Erk pathways negatively regulate matrix mineralization (2007)
  • Author(s): Kono SJ, Oshima Y, Hoshi K, Bonewald LF, Oda H, Nakamura K, Kawaguchi H, Tanaka S.
  • Journal Title: Bone 40 Pages: 68-74
• [Journal Article] Negative feedback loop in the Bim-caspase-3 axis regulating apoptosis and activity of osteoclasts (2007)
  • Author(s): Wakeyama H, Akiyama T, Takahashi K, Amano H, Kadono Y, Nakamura M, Oshima Y, Itabe H, Nakayama KI, Nakayama K, Nakamura K, Tanaka S
  • Journal Title: J Bone Miner Res 22 Pages: 1631-1639
• [Journal Article] Fluoroscopic-based navigation-assisted placement of the tibial tunnel in revision anterior cruciate ligament reconstruction (2007)
  • Author(s): Nakagawa T, Hiraoka H, Fukuda A, Kuribayashi S, Nakayama S, Matsubara T, Nakamura K
  • Journal Title: Arthroscopy 23 : 443 Pages: 1-4
• [Journal Article] Erk pathways negatively regulate matrix mineralization. Bone. 2007, 40:68-74. (2007)
  • Author(s): Kono SJ, Nakamura K, Tanaka S, et. al.
  • Journal Title: Bone 40 Pages: 68-74
• [Journal Article] Negative feedback loop in the Bim-caspase-3 axis regulating apoptosis and activity of osteoclasts. J Bone Miner Res 22:1631-1639. (2007)
  • Author(s): Wakeyama H, Tanaka S, et. al.
  • Journal Title: Journal of Bone and Mineral Research 22 Pages: 1631-1639
• [Journal Article] Negative Regulation of Osteoclastogenesis by Ectodomain Shedding of Receptor Activator of NF-B Ligand. (2006)
  • Author(s): Hikita A, Nakamura K, Tanaka S, et al.
  • Journal Title: Journal of Biological Chemistry 281 Pages: 36846-36855
• [Journal Article] h17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. (2006)
  • Author(s): Sato K, Tanaka S, et al.
  • Journal Title: Journal of Experlmental Medlclne 203 Pages: 2673-2682
• [Journal Article] Force Sensing by Mechanical Extension of the Src Family Kinase Substrate p130Cas. (2006)
  • Author(s): Sawada Y, Tanaka S, et al.
  • Journal Title: Cell 127 Pages: 1015-1026
• [Presentation] 骨破壊を標的にした関節リウマチ治療 (2008)
  • Author(s): 田中栄
  • Organizer: 第26回日本骨代謝学会学術集会
  • Place of Presentation: 大阪ミニシンポジウム6リウマチと骨
  • Year and Date: 2008-10-30
• [Presentation] 関節リウマチにおける骨破壊メカニズム (2008)
  • Author(s): 田中栄
  • Organizer: 第20回中部リウマチ学会
  • Place of Presentation: 浜松
  • Year and Date: 2008-09-06
• [Presentation] 骨吸収を標的にした関節リウマチ治療戦略 (2008)
  • Author(s): 田中栄
  • Organizer: 第52回日本リウマチ学会総会・学術集会ランチョンセミナー13
  • Place of Presentation: 札幌
  • Year and Date: 2008-04-22
• [Presentation] Fluoroscopy based navigationガイド下ACL再建術後に生じたdeep roof impingement phenomenon (2008)
  • Author(s): 中山修一
  • Organizer: JOSKAS
  • Place of Presentation: 東京・高輪
• [Presentation] 関節リウマチにおける骨破壊の機序 (2007)
  • Author(s): 田中栄
  • Organizer: 第22回日本整形外科学会基礎学術集会
  • Place of Presentation: 浜松
  • Year and Date: 2007-10-25
• [Presentation] 脛骨側での膝内側側副靱帯III度損傷の治療 (2007)
  • Author(s): 中山修一
  • Organizer: JOSKAS
  • Place of Presentation: 北海道・札幌
• [Presentation] Fluoroscopic Navigation assisted ACL reconstruction (2007)
  • Author(s): 中山修一
  • Organizer: ISAKOS
  • Place of Presentation: Florence, Italy
• [Presentation] Navigation assisted ACL reconstruction (2006)
  • Author(s): 中山修一
  • Organizer: JOSKAS
  • Place of Presentation: 沖縄・宜野湾市
• [Book] 骨吸収最新整形外科学大系1運動器の生物学と生体力学(中村利孝, 吉川秀樹) (2008)
  • Author(s): 田中栄
  • Publisher: 中山書店東京
• [Book] 新骨の科学(須田立雄, 小澤英浩, 高橋榮明, 田中栄, 中村浩彰, 森諭史) (2007)
  • Author(s): 須田立雄, 小澤英浩, 高橋榮明, 田中栄, 中村浩彰, 森諭史
  • Total Pages: 330
  • Publisher: 医歯薬出版株式会社東京
• [Book] 骨粗鬆症今日の治療指針(山口徹, 北原光夫, 福井次矢) (2007)
  • Author(s): 田中栄
  • Publisher: 医学書院東京