Osteoclastogenesis and subsets of monocytes and macrophages in rheumatoid arthritis

• Project/Area Number: 16K19606
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Nagasaki University
• Principal Investigator: FUKUI Shoichi 長崎大学, 保健・医療推進センター, 助教 (80770833)
• Research Collaborator: KAWAKAMI Atsushi 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90325639) ; IWAMOTO Naoki 長崎大学, 医歯薬学総合研究科(医学系), 助教 (80437897) ; TAMAI Mami 長崎大学, 医歯薬学総合研究科(医学系), 講師 (60380862)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 関節リウマチ / 破骨細胞 / 単球 / 炎症 / IL-6 / 抗CCP抗体 / マクロファージサブセット / 単核球

Outline of Final Research Achievements

We investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC) differentiation ability in patients with rheumatoid arthritis (RA). We investigated the number of M1 or M2 monocytes in peripheral blood mononuclear cells (PBMCs). We also cultured CD14-positive cells from PBMCs and differentiate to OC in vitro. Forty RA patients were included. Twenty-two patients had anti-citrullinated protein antibody (ACPA). There was a positive correlation between the M1/M2 ratio and the differentiated OC number in RA patients. The ACPA-positive patients had significantly higher M1/M2 ratios and greater numbers of OCs than the ACPA-negative patients. The M1/M2 ratio was the sole significant contribution factor to osteoclastogenesis by multivariable regression analysis. RA patients with M1/M2 ratios >1 had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios =<1. M1 and M2 monocyte subsets may become a new target of treatments for RA.

Research Products

• [Journal Article] M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis (2018)
  • Author(s): Fukui Shoichi、Iwamoto Naoki、Takatani Ayuko、Igawa Takashi、Shimizu Toshimasa、Umeda Masataka、Nishino Ayako、Horai Yoshiro、Hirai Yasuko、Koga Tomohiro、Kawashiri Shin-ya、Tamai Mami、Ichinose Kunihiro、Nakamura Hideki、Origuchi Tomoki、Masuyama Ritsuko、Kosai Kosuke、Yanagihara Katsunori、Kawakami Atsushi
  • Journal Title: Frontiers in Immunology Volume: 8 Pages: 1958-1958
  • DOI: 10.3389/fimmu.2017.01958
  • NAID: 120006987316
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] A NOVEL CONCEPT OF M1 AND M2 MONOCYTES IN RHEUMATOID ARTHRITIS: PRO-INFLAMMATORY MONOCYTE POLARIZATION IMBALANCE, ANTI-CITRULLINATED PROTEIN ANTIBODY AND OSTEOCLASTOGENESIS (2017)
  • Author(s): Shoichi Fukui
  • Organizer: Annual European Congress of Rheumatology EULAR 2017
  • Int'l Joint Research
• [Presentation] A novel concept of M1 and M2 monocytes in rheumatoid arthritis; pro-inflammatory monocyte polarization imbalance, anti-citrullinated protein antibody and osteoclastogenesis (2017)
  • Author(s): Shoichi Fukui
  • Organizer: the 61st Annual General Assembly and Scientific Meeting of the Japan College of Rheumatology
• [Presentation] Preferential Distribution of M1 Monocytes in Anti-Cyclic Citrullinated Peptide Antibody Positive Patients with Rheumatoid Arthritis (2016)
  • Author(s): 福井翔一
  • Organizer: アメリカリウマチ学会
  • Place of Presentation: Walter E. Washington Convention Center（アメリカ, ワシントンDC）
  • Int'l Joint Research