A Role of MMP-13 in Inflammatory Bone and Cartilage Destruction

• Project/Area Number: 19591764
• 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: TAKAISHI Hironari Keio University, 医学部, 助教 (60236180)
• Co-Investigator(Kenkyū-buntansha): TOYAMA Yoshiaki 慶應義塾大学, 医学部, 教授 (40129549) ; HORIUCHI Keisuke 慶應義塾大学, 医学部, 講師 (30327564) ; HAKOZAKI Akihiro 慶應義塾大学, 医学部, 嘱託(非常勤) (10365299)
• 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: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 外科 / 再生医学 / 細胞・組織 / 発現制御 / トランスレーショナルリサーチ

Research Abstract

軟骨マトリックスの主要分解酵素であるMMP-13の炎症性骨軟骨破壊における役割を検討した。MMP-13欠損マウス(KO)は野生型と比べて、変形性関節症の誘導には差を認めなかったが、II型コラーゲン抗体カクテル投与による関節炎モデルにおいて亜急性期のミエロイド系細胞の集積および滑膜増生とその後の骨軟骨破壊が抑制されていた。MMP-13は炎症環境下における骨髄由来細胞の末梢への動員および関節炎局所への集積を調節する新規機能をもつ可能性が示唆された。

Research Products

• [Journal Article] IL-27 Abrogates RANKL-mediated Osteoclastogenesis of Human Granulocyte-Macrophage CFU Cells through STAT1-dependent Inhibition of c-Fos (2009)
  • Author(s): Furukawa M, Takaishi H, et al., 11名中2番目
  • Journal Title: J Immunol (in press)
  • Peer Reviewed
• [Journal Article] 1-alpha, 25-dihydroxy vitamin D3 inhibits osteoclastogenesis through IFN-beta-dependent NFATc1 suppression (2009)
  • Author(s): Sakai S, Takaishi H, et al., 13名中2番目
  • Journal Title: J Bone Miner Metab (in press)
  • Peer Reviewed
• [Journal Article] MMP-13 plays a role in keratinocyte migration, angiogenesis and contraction in mouse skin wound healing (2009)
  • Author(s): Hattori N, Mochizuki S, et al., 7名中5番目
  • Journal Title: Am J Pathol (in press)
  • Peer Reviewed
• [Journal Article] Ectodomain shedding of FLT3 ligand is mediated by TACE (2009)
  • Author(s): Horiuchi K, Morioka H, et al., 6名中3番目
  • Journal Title: J Immunol (in press)
  • Peer Reviewed
• [Journal Article] PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblasts (2009)
  • Author(s): Hikata T, Takaishi H, et. al., 14名
  • Journal Title: Blood 113(10) Pages: 2202-2212
  • Peer Reviewed
• [Journal Article] Conditional inactivation of TACE by a Sox9 promoter leads to osteoporosis and increased granulopoiesis via dysregulation of IL-17 and G-CSF (2009)
  • Author(s): Horiuchi K, Kimura T,. et. al., 11名
  • Journal Title: J Immunol 182(4) Pages: 2093-2101
  • Peer Reviewed
• [Journal Article] PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectlyvia osteoblasts. (2009)
  • Author(s): Hikata T, Takaishi H, et . al., 14名中2番目
  • Journal Title: Blood 113 (10) Pages: 2202-2212
  • Peer Reviewed
• [Journal Article] Conditional inactivation of TACE by a Sox9 promoter leads to osteoporosis and increased granulopoiesis via dysregulation of IL-17 and G-CSF. (2009)
  • Author(s): Horiuchi K, Kimura T, ., et. al., 11名中6番目
  • Journal Title: J Immunol 182 (4) Pages: 2093-2101
  • Peer Reviewed
• [Journal Article] Joint diseases and matrix metalloproteinases : a role for MMP-13 (2008)
  • Author(s): Takaishi H, Kimura T, Dalal S, Okada Y, D'Armiento J. 5名
  • Journal Title: Curr Pharm Biotechnol 9 Pages: 47-54
  • Peer Reviewed
• [Journal Article] Growth suppression and apoptosis induction in synovial sarcoma cell lines by a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) (2008)
  • Author(s): Horiuchi K, Morioka H, et. al., 13名
  • Journal Title: Cancer Lett 272 Pages: 336-344
  • Peer Reviewed
• [Journal Article] Growth suppression and apoptosis induction in synovial sarcoma cell lines by a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ). (2008)
  • Author(s): Horiuchi K, Morioka H, et., al., 13名中9番目
  • Journal Title: Cancer Lett 272 Pages: 336-344
  • Peer Reviewed
• [Journal Article] Joint diseases and matrix metalloproteinases : a role for MMP-13. (2008)
  • Author(s): Takaishi H, Kimura T, Dalal S, Okada Y, D'Armiento J.
  • Journal Title: Curr Pharm Biotechnol. 9 Pages: 47-54
  • Peer Reviewed
• [Journal Article] Joint disease and matrix metalloproteinases:a role for MMP-13 (2008)
  • Author(s): Takaishi H, Kimura T, Dalal S, Okada Y, D' Amiento J.
  • Journal Title: Curr Pham Biotechnol 9(1) Pages: 47-54
  • Peer Reviewed
• [Journal Article] Cell surface colony-stimulating factor 1 can be cleaved by TNF-alpha converting enzyme or endocytosed in a clathrin-dependent manner (2007)
  • Author(s): Horiuchi K, Miyamoto T, et al., 13名
  • Journal Title: J Immunol 179 Pages: 6715-6724
  • Peer Reviewed
• [Journal Article] TNF-alpha-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock (2007)
  • Author(s): Horiuchi K, Kimura T, et al., 7名
  • Journal Title: J Immunol 179 Pages: 2686-2689
  • Peer Reviewed
• [Journal Article] Administration of cyclooxygenase-2 inhibitor reduces joint inflammation but exacerbates osteopenia in IL-1 alpha transgenic mice due to GM-CSF overproduction (2007)
  • Author(s): Niki Y, Takaishi H, et al., 8名
  • Journal Title: J Immunol 179 Pages: 639-646
  • Peer Reviewed
• [Journal Article] Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification (2007)
  • Author(s): Morita K, Miyamoto T, et al., 14名
  • Journal Title: J Exp Med 204 Pages: 1613-1623
  • Peer Reviewed
• [Journal Article] Impaired bone fracture healing in matrix metalloproteinase-13 deficient mice (2007)
  • Author(s): osaki N, Takaishi H, et al., 12名
  • Journal Title: Biochem Biophys Res Commun 354 Pages: 846-851
  • Peer Reviewed
• [Journal Article] Cell surface colony-stimulating factor 1 can be cleaved by TNF-alpha converting enzyme or endocytosed in a clathrin-dependent manner (2007)
  • Author(s): Horiuchi K, Miyamoto T, Takaishi H, Hakozaki A, Kosaki N, Miyauchi Y, Furukawa M, Takito J, Kaneko H, Matsuzaki K, Morioka H, Blobel CP, Toyama Y.
  • Journal Title: J Immunol 179(10) Pages: 6715-6724
  • Peer Reviewed
• [Journal Article] Cutting edge:TNF-alpha-converting enzyme(TACE/ADAM17)inactivation in mouse my eloid cells prevents lethality from endotoxin shock (2007)
  • Author(s): Horiuchi K, Kimura T, Miyamoto T, Takaishi H, Okada Y, Toyama Y., Blobel CP.
  • Journal Title: J Immunol 179(5) Pages: 2686-2689
  • Peer Reviewed
• [Journal Article] Administration of cyclooxygenase-2 inhibitor reduces joint inflammation excerbates osteopenia in IL-1 alpha transgenic mice due to GM-CSF overproduction (2007)
  • Author(s): Niki Y, Takaishi H, Takito J, Miyamoto T, Kosaki N, Matsumoto H, Toyama Y, Tada N.
  • Journal Title: J Immunol 179(1) Pages: 639-646
  • Peer Reviewed
• [Journal Article] Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification (2007)
  • Author(s): Morita K, Miyamoto T, Fujita N, Kubota Y, Ito K, Takubo K, Miyamoto K, Ninomiya K, Suzuki T, Iwasaki R, Yai M, Takaishi H, Toyama Y, Suda T.
  • Journal Title: J Exp Med 204(7) Pages: 1613-1623
  • Peer Reviewed
• [Journal Article] Impaired bone frachture healing in matrix metalloproteinase-13 deficient mice (2007)
  • Author(s): Kosaki N, Takaishi H, Kamekura S, Kimura T, Okada Y, Minqi L, Amizuka N, Chung UI, Nakamura K, Kawaguchi H, Toyama Y, D' Armiento J.
  • Journal Title: Biochem Biophys Res Commun 354(4) Pages: 846-851
  • Peer Reviewed
• [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] STAT1ノックアウトマウスでは骨折後の膜性骨化と仮骨リモデリングが亢進する (2008)
  • Author(s): 田島康介(TAJIMA KOSUKE)
  • 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] MEK5-ERK5経路はRANKL依存性の破骨細胞分化を制御する (2008)
  • Author(s): 内川伸一(UTIKAWA SHINICHI)
  • 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] IL-27/WSX-1シグナルはLPS刺激によって誘導され、RANKL依存性の破骨細胞形成をSTAT1の活性化を介して抑制する (2008)
  • Author(s): 古川満(FURUKAWA MITSURU)
  • 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] トランスジェニックマウスは破骨細胞の分化障害により骨量増加を示す (2008)
  • Author(s): 日方智宏(HIKATA TOMOHIRO)
  • 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)ERa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
  • 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] STAT1ノックアウトマウスでは骨折後の膜性骨化と仮骨リモデリングが亢進する (2008)
  • Author(s): 田島 康介
  • 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] MEK5-ERK5経路はRANKL依存性の破骨細胞分化を制御する (2008)
  • Author(s): 内川 伸一
  • 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] IL-27/WSX-1シグナルはLPS刺激によって誘導され、RANKL依存性の破骨細胞形成をSTAT1の活性化を介して抑制する (2008)
  • Author(s): 古川 満
  • 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] トランスジェニツクマウスは破骨細胞の分化障害により骨量増加を示す (2008)
  • Author(s): 日方 智宏
  • 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] マトリックスメタロプロテアーゼ-13(MMP-13)欠損マウスでは巣状糸球体硬化症の発症が抑制される (2008)
  • Author(s): 坂巻裕介(SAKAMAKI YUSUKE)
  • Organizer: 第51回日本腎臓学会学術総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-05-31
• [Presentation] マトリツクスメタロプロテアーゼー13(MMP-13)欠損マウスでは巣状糸球体硬化症の発症が抑制される (2008)
  • Author(s): 坂巻 裕介
  • Organizer: 第51回 日本腎臓学会学術総会
  • Place of Presentation: 福岡国際会館
  • Year and Date: 2008-05-31