The mechanism of dendritic cell-derived osteoclasts in the pathogenesis of arthritis.

• Project/Area Number: 16K09915
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: Hanami Kentaro 産業医科大学, 医学部, 助教 (50441853)
• Co-Investigator(Kenkyū-buntansha): 久保 智史 産業医科大学, 医学部, 助教 (70461548)
• Project Period (FY): 2016-10-21 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 樹状細胞 / 破骨細胞 / 抗原提示能 / シグナル伝達

Outline of Final Research Achievements

We reported that human DCs can differentiate into (dendritic derived osteolast; DCOC) in the inflammatory lesion without being regulated by osteoblasts/osteocytes. DCOC possess not only the bone resorption ability but also the antigen-presenting function as DC. Actually, there were characteristic osteoclasts bearing costimulatory molecules in RA synovium, indicating that DCOC may play a pivotal role in the pathogenesis of RA by the maintenance of inflammation as well as joint destruction.

Academic Significance and Societal Importance of the Research Achievements

樹状細胞由来破骨細胞(dendritic derived osteolast; DCOC)は骨破壊に重要な役割を担うと共に、炎症性病態における免疫応答にも関与している可能性が考えられる。本研究では、関節リウマチ患者滑膜にDCOCが存在する事を示し、DCOCの分化機序の解明、DCOC機能と関節破壊・関節炎の関連を解明した事で、関節炎病態に対するより有効的な治療戦略を展開出来ると考えられ、医学的にも多大な意義を持つものと考える。

Research Products

• [Journal Article] Effectiveness and safety of hydroxychloroquine therapy with or without corticosteroid in patients with systemic lupus erythematosus. (2019)
  • Author(s): Miyagawa I, Nakano K, Nakayamada S, Iwata S, Hanami K, Fukuyo S, Kubo S, Inoue Y, Ueno M, Tanaka Y.
  • Journal Title: Int J Rheum Dis. Volume: 22(3) Issue: 3 Pages: 434-442
  • DOI: 10.1111/1756-185x.13387
  • Peer Reviewed / Open Access
• [Journal Article] Relevance of interferon-gamma in pathogenesis of life-threatening rapidly progressive interstitial lung disease in patients with dermatomyositis. (2018)
  • Author(s): Ishikawa Y, Iwata S, Hanami K, Nawata A, Zhang M, Yamagata K, Hirata S, Sakata K, Todoroki Y, Nakano K, Nakayamada S, Satoh M, Tanaka Y.
  • Journal Title: Arthritis Res Ther Volume: 20 Issue: 1 Pages: 240-240
  • DOI: 10.1186/s13075-018-1737-2
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of efficacy of TNF inhibitors and abatacept in patients with rheumatoid arthritis; Adjusted with propensity score matching. (2018)
  • Author(s): Kubo S, Nakayamada S, Nakano K, Sawamukai N, Hirata S, Hanami K, Saito K1, Tanaka Y.
  • Journal Title: Clin Immunol. Volume: 191 Pages: 67-74
  • DOI: 10.1016/j.clim.2018.03.018
  • Peer Reviewed / Open Access
• [Journal Article] Pleurisy Caused by <i>Mycobacterium abscessus</i> in a Young Patient with Dermatomyositis: A Case Report and Brief Review of the Literature (2018)
  • Author(s): Noguchi S, Hanami K, Miyata H, Torii R, Shimabukuro I, Kubo S, Obata H, Yoshii C, Yatera K.
  • Journal Title: Internal Medicine Volume: 57 Issue: 7 Pages: 997-1002
  • DOI: 10.2169/internalmedicine.9537-17
  • NAID: 130006602626
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Peripheral Immunophenotyping Identifies Three Subgroups Based on T Cell Heterogeneity in Lupus Patients. (2017)
  • Author(s): Kubo S, Nakayamada S, Yoshikawa M, Miyazaki Y, Sakata K, Nakano K, Hanami K, Iwata S, Miyagawa I, Saito K, Tanaka Y.
  • Journal Title: Arthritis Rheumatol. Volume: 69(10) Issue: 10 Pages: 2029-2037
  • DOI: 10.1002/art.40180
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association of the multi-biomarker disease activity score with joint destruction in patients with rheumatoid arthritis receiving tumor necrosis factor-alpha inhibitor treatment in clinical practice. (2016)
  • Author(s): Hirata S, Li W, Kubo S, Fukuyo S, Mizuno Y, Hanami K, Sawamukai N, Yamaoka K, Saito K, Defranoux NA, Tanaka Y.
  • Journal Title: Mod Rheumatol Volume: 26 Issue: 6 Pages: 850-856
  • DOI: 10.3109/14397595.2016.1153449
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Comparison of the efficacies of abatacept and tocilizumab in patients with rheumatoid arthritis by propensity score matching. (2015)
  • Author(s): Kubo S, Nakayamada S, Nakano K, Hirata S, Fukuyo S, Miyagawa I, Hanami K, Saito K, Tanaka Y.
  • Journal Title: Ann Rheum Dis. Volume: Aug 5 Issue: 7 Pages: 207784-207784
  • DOI: 10.1136/annrheumdis-2015-207784
  • Peer Reviewed / Open Access / Int'l Joint Research