フルテキストファイル
著者
Funaki Yoshihiro Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine, 鳥取大学研究者総覧
Hasegawa Yasuyuki Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
Okazaki Ryota Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine, 鳥取大学研究者総覧
Yamasaki Akira Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine, 鳥取大学研究者総覧 KAKEN研究者をさがす
Sueda Yuriko Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
Yamamoto Akihiro Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine, 鳥取大学研究者総覧
Yanai Masaaki Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
Fukushima Takehito Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
Harada Tomoya Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine, 鳥取大学研究者総覧
Makino Haruhiko Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine, 鳥取大学研究者総覧 KAKEN研究者をさがす
Shimizu Eiji Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine, KAKEN研究者をさがす
キーワード
interleukin-17
osteoblasts
osteoclasts
RANK ligand
resolvin E1
抄録
【Background】 Resolvin E1 (RvE1) derived from the ω-3 polyunsaturated fatty acid eicosapentaenoic acid is known to be a potent pro-resolving lipid mediator that prevents chronic inflammation and osteoclastogenesis. We investigated the inhibitory effects of RvE1 on osteoclastogenesis
and bone resorption to clarify its therapeutic potential for rheumatoid arthritis (RA).
【Methods】 Receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation was assessed with tartrate-resistant acid phosphatase staining.
RANKL-induced bone resorption was assessed by the measurement of pit formation using calcium phosphate-labeled fluorescent polyanionic molecules in RAW264.7 cells as osteoclast precursors. The effects of RvE1 on the RANKL-induced mRNA expression of osteoclast-specific genes and transcriptional factors such as c-fos and nuclear factor of activated T cells c1 (NFATc1) in RAW264.7 cells were measured by quantitative real-time PCR. The distribution of NFATc1 induced by RANKL was evaluated by immunofluorescence staining in RAW264.7 cells. To analyze the mechanism of the inhibitory effect of RvE1 on osteoclastogenesis, we measured IL-17-induced RANKL mRNA expression in MC3T3-E1 osteoblast cells treated with RvE1 using quantitative real-time PCR and determined the level of prostaglandin E2 (PGE2) production by enzyme-linked immunosorbent assay.
【Results】 RvE1 significantly suppressed RANKL-induced osteoclast differentiation and bone resorption. RvE1 inhibited the RANKL-induced mRNA expression of osteoclast-specific genes along with the transcription factors NFATc1 and c-fos. Moreover, NFATc1 translocation from the cytoplasm to the nucleus of RAW264.7 cells was suppressed following RvE1 treatment. RvE1 also inhibited IL-17-induced RANKL mRNA expression and PGE2 production in MC3T3-E1 cells.
【Conclusion】 RvE1 inhibited osteoclastogenesis and bone resorption by suppressing RANKL-induced NFATc1 and c-fos expression in osteoclasts and IL-17-induced RANKL expression through the autocrine action of PGE2 in osteoblasts. Our data suggest RvE1 as a new therapeutic target of RA.
出版者
Tottori University Faculty of Medicine
資料タイプ
学術雑誌論文
ISSN・ISBN
1346-8049
書誌ID
AA00892882
掲載誌名
Yonago Acta Medica
最新掲載誌名
Yonago Acta Medica
61
1
開始ページ
8
終了ページ
18
発行日
2018-03-28
著者版フラグ
出版社版
掲載情報
Yonago Acta Medica. 2018, 61(1), 8-18
部局名
医学部・医学系研究科・医学部附属病院
言語
英語