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2017 Fiscal Year Annual Research Report

Innate immunity reaction in marcophage for periprosthetic joint infection

Research Project

Project/Area Number 15K10459
Research InstitutionYamagata University

Principal Investigator

高木 理彰  山形大学, 医学部, 教授 (40241707)

Co-Investigator(Kenkyū-buntansha) 佐々木 幹  山形大学, 医学部, 非常勤講師 (00444034)
高窪 祐弥  山形大学, 医学部, 准教授 (80431641)
Project Period (FY) 2015-04-01 – 2018-03-31
Keywords人工関節 / 自然免疫 / マクロファージ / Toll様受容体 / Nod様受容体 / 人工関節感染
Outline of Annual Research Achievements

本邦における65歳以上の人口は過去10年で全人口の17.5%から24.1%と急激に増加している。米国における報告では、高齢人口の増加に伴って人工股関節全置換術は、2010年に65.5万件であったものが2020年には137.6万件に増加すると予想されている。しかし、インプラント感染症や非感染性の骨溶解と弛みの問題は未だ長期成績に大きく影響しているが、インプラント感染症に対する生体反応機構には未だ不明な点が多い。
本研究では、昨年までにリボタイコ酸を用いたマクロファージ刺激試験においてNod 様受容体発現が亢進すること、向炎症性サイトカインであるTNF-alpha発現・分泌が亢進する一方で、IL-1betaの発現は遺伝子レベルで亢進するものの分泌されない現象を明らかにした。最終年の本年は、LPSおよび非メチル化CpG DNAを用いたマクロファージ刺激試験においてToll様受容体, Nod 様受容体及びそれらのアダプター関連分子の発現動態を解析した。また、感染性人工関節周囲組織におけるToll様受容体、Nod 様受容体並びにアダプター関連分子の組織及び細胞局在を病理学的に検討し、非感染性弛緩人工関節周囲組織、変形性関節症、関節リウマチ滑膜組織と比較した。
種々の炎症病態に深く関与する自然免疫系受容体、特にマクロファージに発現するToll様受容体とNod 様受容体に着目し、これらの関連分子の組織局在と機能解析を行った。これらの人工関節インプラント感染症における生体反応機構を解明することにより、人工関節感染症の発生や病態の進行を抑制することで、人工関節の長期成績が向上すると期待されている。

  • Research Products

    (19 results)

All 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (2 results)

  • [Int'l Joint Research] Stanford 大学(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      Stanford 大学
  • [Journal Article] Immunohistochemical Analysis of Inflammatory Rheumatoid Synovial Tissues Using Anti-Human Podoplanin Monoclonal Antibody Panel.2018

    • Author(s)
      Suzuki T, Takakubo Y, Oki H, Liu X, Honma R, Naganuma Y, Goodman SB, Kaneko MK, Kato Y, Takagi M.
    • Journal Title

      Monoclon Antib Immunodiagn Immunother.

      Volume: 37 Pages: 12-19

    • DOI

      10.1089/mab.2017.0047.

    • Peer Reviewed
  • [Journal Article] Activation of plasmacytoid dendritic cells by apoptotic particles - mechanism for the loss of immunological tolerance in Sjögren's syndrome.2018

    • Author(s)
      Ainola M, Porola P, Takakubo Y, Przybyla B, Kouri VP, Tolvanen TA, Hänninen A, Nordström DC.
    • Journal Title

      Clin Exp Immunol.

      Volume: 191 Pages: 301-310

    • DOI

      10.1111/cei.13077.

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Danger of frustrated sensors: Role of Toll-like receptors and NOD-like receptors in aseptic and septic inflammations around total hip replacements.2017

    • Author(s)
      Takagi M, Takakubo Y, Pajarinen J, Naganuma Y, Oki H, Masahiro M, Goodman S
    • Journal Title

      J Orthop Translat

      Volume: 10 Pages: 1-8

    • DOI

      10.1016/j.jos.2018.01.016.

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Incidence of Atypical Femoral Fractures in Patients with Rheumatic Disease: Yamagata Prefectural Committee of Atypical Femoral Fractures (YamaCAFe) Study.2017

    • Author(s)
      Takakubo Y, Ohta D, Ishi M, Takagi M, et al.
    • Journal Title

      Tohoku J Exp Med.

      Volume: 242 Pages: 327-334

    • DOI

      10.1620/tjem.242.327.

    • Peer Reviewed
  • [Journal Article] DGKζ downregulation enhances osteoclast differentiation and bone resorption activity under inflammatory conditions.2017

    • Author(s)
      Iwazaki K, Takana T, Hozumi Y, Okada M, Tsuchiya R, Iseki K, Topham MK, Kawamae K, Takagi M, Goto K
    • Journal Title

      J Cellular physiol

      Volume: 232 Pages: 617-624

    • DOI

      10.1002/jcp.25461

    • Peer Reviewed
  • [Journal Article] 3)Kaneko MK**, Nakamura T**, Honma R, Ogasawara S**, Fujii Y**, Abe S**, Takagi M, Harada H**, Suzuki H**, Nishioka Y**, Kato Y**: Development and characterization of anti-glycopeptide monoclonal antibodies against human podoplanin, using glycan-deficient cell lines generated by CRISPR/Cas9 and TALEN.2017

    • Author(s)
      Kaneko MK, Nakamura T, Honma R, Ogasawara S, Fujii Y, Abe S, Takagi M, Harada H, Suzuki H, Nishioka Y, Kato Y
    • Journal Title

      Cancer Medicine

      Volume: 6 Pages: 382-396

    • DOI

      10.1002/cam4.954

    • Peer Reviewed
  • [Journal Article] Characterization of the Anti-Bovine Podoplanin Monoclonal Antibody PMab-44.2017

    • Author(s)
      Yamada S, Honma R, Kaneko MK, Nakamura T, Yanaka M, Saidoh N, Takagi M, Konnai S, Kato Y.
    • Journal Title

      Monoclon Antib Immunodiagn Immunother.

      Volume: 36 Pages: 129-134

    • DOI

      10.1089/mab.2017.0016

    • Peer Reviewed
  • [Journal Article] Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity.2017

    • Author(s)
      Kato Y, Kunita A, Fukayama M, Abe S, Nishioka Y, Uchida H, Tahara H, Yamada S, Yanaka M, Nakamura T, Saidoh N, Yoshida K, Fujii Y, Honma R, Takagi M, Ogasawara S, Murata T, Kaneko MK.
    • Journal Title

      Monoclon Antib Immunodiagn Immunother.

      Volume: 36 Pages: 20-24

    • DOI

      10.1089/mab.2016.0045.

    • Peer Reviewed
  • [Journal Article] The bone regeneration using bone marrow-derived mesenchymal stem call with recombinant human bone morphogenetic protein-2 in oallogeneic repair model of femoral segmental defect of rats.2017

    • Author(s)
      Takano M, Hashimoto J, Tsuchida H, Takagi M
    • Journal Title

      Yamagata Med J.

      Volume: 35 Pages: 90-100

    • Peer Reviewed
  • [Journal Article] Treatment for ulnar neuritis around the elbow in adolescent baseball players: Factors associated with poor outcome.2017

    • Author(s)
      Maruyama M, Satake H, Takahara M, Harada M, Uno T, Mura N, Takagi M
    • Journal Title

      Am J Sports Med

      Volume: 45 Pages: 803-809

    • DOI

      10.1177/0363546517721188

    • Peer Reviewed
  • [Journal Article] The bone regeneration using bone marrow-derived mesenchymal stem call with recombinant human bone morphogenetic protein-2 in oallogeneic repair model of femoral segmental defect of rats.2017

    • Author(s)
      Yamakawa J, Hashimoto J, Takao M, Takagi M
    • Journal Title

      Open Orthop J

      Volume: 11 Pages: 1-12

    • DOI

      10.2174/1874325001711010001

    • Peer Reviewed / Open Access
  • [Presentation] International medical support in the disaster experience from Nepal big earthquake 20152017

    • Author(s)
      Takagi M, Kasai Y, Itoi E, Iwamoto Y, Yamagata T, Saiki K, Yonezawa T
    • Organizer
      The 90th Annual Meeting of the Japanese Orthopaedic Association
    • Invited
  • [Presentation] Postoperative rehabilitation of atypical femoral fractures in patients with rheumatic diseases2017

    • Author(s)
      Takakubo Y, Sasaki K, Narita Atsushi, Narita Aya, Kanauti Y, Yamakawa J, Sugawara M, Kobayashi S, Hanaka N, Takagi M
    • Organizer
      The 54th Annual meeting of the Japanese association of rhehabilitation medicine
  • [Presentation] Is increasing the trend of primary total hip arthroplasties for the patients with osteoarthritis, but decreasing the rate of female in super-aging area of Japan in last twelve years?2017

    • Author(s)
      Takakubo Y, Sasaki K, Oki H, Naganuma Y, Narita A, Hirayama T, Tamaki Y, Takagi Y
    • Organizer
      EULAR 2017
    • Int'l Joint Research
  • [Presentation] Trend of total hip arthroplasties in the super-aging area in Northern Japan.2017

    • Author(s)
      Takakubo Y, Sasaki K, Ito J, Oki H, Honma R, Kawaji H, Ishii M, Takagi M
    • Organizer
      ISTA 2017
    • Int'l Joint Research
  • [Presentation] The incidence of atypical femoral fractures in patients with rheumatic disease in our prefectural area of north Japan in the suger-aging society: YamaCAFe study2017

    • Author(s)
      Takakubo Y, Ohta D, Okuda S, Ito J, Oki H, Naganuma Y, Sasaki K, Ishii M, Takagi M
    • Organizer
      The 90th Annual Meeting of the Japanese Orthopaedic Association
  • [Book] 避難生活で起こりやすい廃用症候群を防ぐために -災害リハビリテーションとは-2018

    • Author(s)
      高木理彰
    • Total Pages
      2
    • Publisher
      MedicalNote
  • [Book] 変形性関節症(股関節)の手術療法 ~骨切り術から人工股関節置換術まで~2017

    • Author(s)
      高窪祐弥, 佐々木幹, 高木理彰
    • Total Pages
      9
    • Publisher
      Pharma Medica

URL: 

Published: 2018-12-17  

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