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M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

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Title: M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis
Authors: 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
Issue Date: 8-Jan-2018
Publisher: Frontiers Media S.A.
Citation: Frontiers in Immunology, 8, 1958; 2018
Abstract: Objectives: We investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC) differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA). Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro. Results: Forty RA patients and 20 healthy donors were included. Twenty-two patients (55%) were anticitrullinated protein antibody (ACPA) positive. The median M1/M2 ratio was 0.59 (0.31-1.11, interquartile range). There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001). The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028) and significantly greater numbers of OCs in vitro (p = 0.005) than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios > 1 (having relatively more M1 monocytes) had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes. Conclusion: M1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.
URI: http://hdl.handle.net/10069/38250
DOI: 10.3389/fimmu.2017.01958
Rights: © 2018 Fukui, Iwamoto, Takatani, Igawa, Shimizu, Umeda, Nishino, Horai, Hirai, Koga, Kawashiri, Tamai, Ichinose, Nakamura, Origuchi, Masuyama, Kosai, Yanagihara and Kawakami. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/38250

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