Resolvin E1 Inhibits Osteoclastogenesis and Bone Resorption by Suppressing IL-17-induced RANKL Expression in Osteoblasts and RANKL-induced Osteoclast Differentiation

URI http://repository.lib.tottori-u.ac.jp/Repository/metadata/5536
本文ファイル
タイトル
Resolvin E1 Inhibits Osteoclastogenesis and Bone Resorption by Suppressing IL-17-induced RANKL Expression in Osteoblasts and RANKL-induced Osteoclast Differentiation
タイトル読み
タイトルその他
著者
著者 Funaki Yoshihiro
著者読み
著者英語Author Funaki Yoshihiro
所属Affiliation Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
著者 Hasegawa Yasuyuki
著者読み
著者英語Author Hasegawa Yasuyuki
所属Affiliation Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
著者 Okazaki Ryota
著者読み
著者英語Author Okazaki Ryota
所属Affiliation Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
著者 Yamasaki Akira
著者読み
著者英語Author Yamasaki Akira
所属Affiliation Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
著者 Sueda Yuriko
著者読み
著者英語Author Sueda Yuriko
所属Affiliation Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
著者 Yamamoto Akihiro
著者読み
著者英語Author Yamamoto Akihiro
所属Affiliation Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
著者 Yanai Masaaki
著者読み
著者英語Author Yanai Masaaki
所属Affiliation Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
著者 Fukushima Takehito
著者読み
著者英語Author Fukushima Takehito
所属Affiliation Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
著者 Harada Tomoya
著者読み
著者英語Author Harada Tomoya
所属Affiliation Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
著者 Makino Haruhiko
著者読み
著者英語Author Makino Haruhiko
所属Affiliation Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
著者 Shimizu Eiji
著者読み
著者英語Author Shimizu Eiji
所属Affiliation Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine,
キーワード
interleukin-17
osteoblasts
osteoclasts
RANK ligand
resolvin E1
NDC分類
4類 自然科学
内容

【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
紀要論文
外部リンク
ISSN/ISBN
0513-5710
書誌ID
AA00892882
掲載誌・書籍タイトル
Yonago Acta Medica
61
1
開始ページ
8
終了ページ
18
発行日
2018-03-28
DOI
出版社版
著作権表記
掲載情報

Yonago Acta Medica. 2018, 61(1), 8-18

学部学科区分
医学研究科・医学部
本文言語
英語
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