Innate immunity reaction in marcophage for periprosthetic joint infection

• Project/Area Number: 15K10459
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Yamagata University
• Principal Investigator: Takagi Michiaki 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
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 人工関節 / インプラント感染症 / 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 Final Research Achievements

One of big problems is periprosthetic joint infection (PJI) in total joint arthroplasty. PJI cause a severe loosening of implant. Innate immunity and its effector mechanism with immune sensors, Toll-like receptor (TLR) and Nod-like receptor (NLR) at the forefront of host defense. We’ve reported the presenting of several TLRs and NLRs in macrophages of septic granuloma. We summarized TLRs and NLRs in septic THA. When TLRs recognized abnormal antigens, they stimulate production of proinflammatory cytokines and inflammasome.
Innate sensors including TLRs or NLRs were well-equipped in each subset of macrophage in septic loosening tissues around artificial hip joint in different manner depending on the pathologic conditions.

Research Products

• [Int'l Joint Research] Stanford 大学(米国)
• [Int'l Joint Research] ヘルシンキ大学(フィンランド)
• [Int'l Joint Research] スタンフォード大学(米国)
• [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 Issue: 1 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 Issue: 3 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 Issue: 3 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, et al.
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 242 Issue: 4 Pages: 327-334
  • DOI: 10.1620/tjem.242.327
  • NAID: 130006067688
  • ISSN: 0040-8727, 1349-3329
  • 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 Issue: 3 Pages: 617-624
  • DOI: 10.1002/jcp.25461
  • Peer Reviewed
• [Journal Article] 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 Med. Volume: 6(2) Issue: 2 Pages: 382-396
  • DOI: 10.1002/cam4.954
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Characterization of the Anti-Bovine Podoplanin Monoclonal Antibody PMab-44. (2017)
  • Author(s): Yamada, S., Honma, R., Kaneko, M. K., Nakamura, T., Yanaka, M., Saidoh, N., Takagi, M., Konnai, S. and Kato, Y.
  • Journal Title: Monoclon. Antib. Immunodiagn. Immunother. Volume: 36 Issue: 3 Pages: 129-134
  • DOI: 10.1089/mab.2017.0016
  • Peer Reviewed / Open Access
• [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(1) Issue: 1 Pages: 20-24
  • DOI: 10.1089/mab.2016.0045
  • Peer Reviewed / Acknowledgement Compliant
• [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] Comparison of the Effects of Osteochondral Autograft Transplantation With Platelet-Rich Plasma or Platelet-Rich Fibrin on Osteochondral Defects in a Rabbit Model. (2017)
  • Author(s): Maruyama M, Takakubo Y, et al.
  • Journal Title: Am J Sports Med. Volume: 45 Issue: 14 Pages: 3280-3288
  • 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 Issue: 1 Pages: 1-12
  • DOI: 10.2174/1874325001711010001
  • Peer Reviewed / Open Access
• [Journal Article] Distribution of podoplanin in synovial tissues in rheumatoid arthritis patients using biologic or conventional disease-modifying anti-rheumatic drugs. (2017)
  • Author(s): Takakubo Y, Oki H, Naganuma Y, Sasaki K, Sasaki A, Tamaki Y, Suran Y, Konta T, Takagi M
  • Journal Title: Curr Rheumatol Rev Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll-like receptor 2 cascade and inflammasomes. (2016)
  • Author(s): Naganuma Y, Takakubo Y, Takagi M, et al
  • Journal Title: Journal of Biomedical Material and Research A Volume: 104 Issue: 2 Pages: 435-444
  • DOI: 10.1002/jbm.a.35581
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 過去11年間の人工股関節手術件数の推移 -当院と関連病院の傾向と特徴- (2016)
  • Author(s): 高窪祐弥, 伊藤重治, 佐々木幹, 平山朋幸, 大木弘治, 門馬亮介, 玉木康信, 川路博之, 小林真司, 石井政次, 高木理彰
  • Journal Title: Hip joint Volume: 42 Pages: 912-914
  • Peer Reviewed
• [Journal Article] トシリズマブ使用関節リウマチ患者における人工関節手術の検討 (2016)
  • Author(s): 高窪祐弥, 大石隆太, 伊藤重治, 長沼靖, 梁秀蘭, 佐々木明子, 佐々木幹, 大類広, 高木理彰
  • Journal Title: 日人工関節会誌 Volume: 46 Pages: 633-634
• [Journal Article] 精神疾患を有する患者に対する人工股関節全置換術の周術期合併症と短期成績 (2016)
  • Author(s): 竹内隆二, 佐々木幹, 高窪祐弥, 伊藤重治, 平山朋幸, 大木弘治, 高木理彰
  • Journal Title: Hip joint Volume: ４２ Pages: 944-946
  • Peer Reviewed
• [Journal Article] Modulation of mouse macrophage polarization in vitro using IL-4 delivery by osmotic pumps. (2015)
  • Author(s): Pajarinen J, Takagi M, Goodman SB, et al
  • Journal Title: J Biomed Mater Res A Volume: 103 Issue: 4 Pages: 1339-1345
  • DOI: 10.1002/jbm.a.35278
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 過去10年間の人工関節手術件数の推移-当院と関連病院の傾向と特徴- (2015)
  • Author(s): 高窪祐弥, 佐々木幹, 高木理彰ほか
  • Journal Title: 日本人工関節会誌 Volume: 45 Pages: 773-774
  • Peer Reviewed
• [Journal Article] PJIの病理組織学的検討. (2015)
  • Author(s): 高窪祐弥, 佐々木幹, 高木理彰ほか
  • Journal Title: 関節外科 Volume: 34 Pages: 35-41
• [Presentation] International medical support in the disaster experience from Nepal big earthquake 2015 (2017)
  • 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 diseases (2017)
  • 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 study (2017)
  • 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
• [Presentation] Current knowledge of implant-related pathology. (2016)
  • Author(s): Takagi M
  • Organizer: 2016 International Comibned Meeting of Orthopaedic Research Societies
  • Place of Presentation: Convention center (Xi’an, Chaina)
  • Year and Date: 2016-09-22
  • Int'l Joint Research / Invited
• [Presentation] The effect of anti-TNF inhibitors on innate immune system in synovial tissues in rheumatoid arthritis patients (2016)
  • Author(s): Takakubo Y, Oki H, Yang S, Hanaka N, Sasaki A, Ito J, L Xing, Sasaki K, Takagi M
  • Organizer: 2016 International Comibned Meeting of Orthopaedic Research Societies
  • Place of Presentation: Convention center (Xi’an, Chaina)
  • Year and Date: 2016-09-22
  • Int'l Joint Research
• [Presentation] A platelet aggregation-inducing factor podoplanin is highly expressed metastatic legions of osteosarcoma (2016)
  • Author(s): Oki H, Yang S, Hanaka N, Sasaki A, Ito J, L Xing, Sasaki K, Takagi M
  • Organizer: 2016 International Comibned Meeting of Orthopaedic Research Societies
  • Place of Presentation: Convention center (Xi’an, Chaina)
  • Year and Date: 2016-09-22
  • Int'l Joint Research
• [Presentation] Normative data of key and pulp pinches to grip strength in healthy twenties (2016)
  • Author(s): Hanaka N, Sasaki A, Ito J, L Xing, Sasaki K, Takagi M
  • Organizer: 2016 International Comibned Meeting of Orthopaedic Research Societies
  • Place of Presentation: Convention center (Xi’an, Chaina)
  • Year and Date: 2016-09-22
  • Int'l Joint Research
• [Presentation] Trend of atypical femoral fractures in rheumatic patients in the highly super aging area of North Japan (2016)
  • Author(s): Takakubo Y, Ota D, Naganuma Y, Oki H, Narita A, Ito J, Sasaki K, Takagi M
  • Organizer: European League Against Rheumatism 2016
  • Place of Presentation: Excell center (London, UK)
  • Year and Date: 2016-06-07
  • Int'l Joint Research
• [Presentation] Innate immune system in total joint replacement (2016)
  • Author(s): Takagi M
  • Organizer: The 9th Clare Valley Bone Meeting, Clare Valley
  • Place of Presentation: Clare Convention Centre （Clare Valley, Australia）
  • Year and Date: 2016-04-03
  • Int'l Joint Research / Invited
• [Presentation] Outcome of rotational acetabular osteotomy for dysplastic follow up for minimum 15 years (2016)
  • Author(s): Sasaki K, Ida H, Ishii M, Kawaji H, Takakubo Y, Ito J, Monma R, Takagi M
  • Organizer: The 9th Clare Valley Bone Meeting, Clare Valley
  • Place of Presentation: Clare Convention Centre （Clare Valley, Australia）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] The relationship between reduction pattern and sliding distance in AO/OTA 31-A2/A3 trochanteric fractures in the elderly (2016)
  • Author(s): Ito J, Sasaki K, Takakubo Y, Momma R, Takagi M
  • Organizer: The 9th Clare Valley Bone Meeting, Clare Valley
  • Place of Presentation: Clare Convention Centre （Clare Valley, Australia）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Expression of Toll-like receptors and distribution of immune-cells in rheumatoid synovial tissues of the patients treated by Abatacept (2016)
  • Author(s): Takakubo Y, Naganuma Y, Oki H, Yang S, Sasaki K, Takagi M
  • Organizer: European League Against Rheumatism 2016
  • Place of Presentation: Excell center (London, UK)
  • Int'l Joint Research
• [Presentation] 過去11年間の人工股関節手術件数の推移 -当院と関連病院の傾向と特徴- (2015)
  • Author(s): 高窪祐弥, 佐々木幹, 高木理彰ほか
  • Organizer: 第42回日本股関節学会学術集会
  • Place of Presentation: グランフロント大阪, 大阪市, 大阪
  • Year and Date: 2015-10-30
• [Presentation] 過去11年間の人工股関節手術件数の推移-当院と関連病院の傾向と特徴- (2015)
  • Author(s): 高窪祐弥, 佐々木幹, 高木理彰ほか
  • Organizer: 第42回日本股関節学会学術集会
  • Place of Presentation: グランフロント大阪, 大阪市, 大阪
  • Year and Date: 2015-10-30
• [Presentation] 無菌性弛緩人工股関節の病態におけるNLPR3の関与 (2015)
  • Author(s): 高窪祐弥, 佐々木幹, 高木理彰ほか
  • Organizer: 第30回日本整形外科学会基礎学術集会
  • Place of Presentation: 富山国際会議場, 富山市, 富山
  • Year and Date: 2015-10-22
• [Presentation] 当科における人工股関節感染予防の取り組みと感染率の変化 (2015)
  • Author(s): 佐々木幹, 高窪祐弥, 高木理彰ほか
  • Organizer: 第88回日本整形外科学会学術総会
  • Place of Presentation: 神戸ポートピアホテル, 神戸市, 兵庫
  • Year and Date: 2015-05-21
• [Presentation] Danage-associated molecular patterns(damps) of toll-like receptors in aseptic loosened total hip arthroplasty. (2015)
  • Author(s): Takakubo Y, Sasaki K, Takagi M, et al
  • Organizer: ORS annual meeting
  • Place of Presentation: MGM Grand Hotel, Las Vegas, NV, USA
  • Year and Date: 2015-04-01
  • Int'l Joint Research
• [Presentation] Immunohistochemical localization and cellular reaction of Tlr2 and Nlrp3 cascades in aseptic loosening of totally hip joints. (2015)
  • Author(s): Takakubo Y, Sasaki K, Takagi M, et al
  • Organizer: ORS annual meeting
  • Place of Presentation: MGM Grand Hotel, Las Vegas, NV, USA
  • Year and Date: 2015-04-01
  • Int'l Joint Research
• [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
• [Book] 整形外科SURGICAL TECHNIQUE BOOKS 3 人工股関節置換術［THA・BHA］ (2016)
  • Author(s): 高木理彰
  • Total Pages: 5
  • Publisher: 大阪, メディカ出版
• [Book] 膠原病・リウマチ・アレルギー 研修ノート (2016)
  • Author(s): 高木理彰
  • Total Pages: 5
  • Publisher: 診断と治療社
• [Book] 今日の整形外科治療方針 (2016)
  • Author(s): 高木理彰
  • Total Pages: 5
  • Publisher: 医学書院
• [Book] 標準整形外科学 (2016)
  • Author(s): 高木理彰
  • Total Pages: 4
  • Publisher: 医学書院