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ID 114641
タイトル別表記
S100A9は、骨細胞様細胞においてMAPKsおよびSTAT3シグナル伝達経路を介してIL-6およびRANKLの発現を増加させる
著者
高木, 亮輔 徳島大学大学院口腔科学教育部(口腔科学専攻)
キーワード
Osteocyte
Calprotectin
S100A9
IL-6
RANKL
資料タイプ
学位論文
抄録
Objective: Calprotectin is hetero-complex of S100A8 and S100A9 and mainly secreted from neutrophils, monocytes and chondrocytes in inflammatory condition. Calprotectin binds to RAGE and TLR4, and induces the expression of pro-inflammatory chemokines and cytokines in various cells. Periodontitis is chronic inflammatory disease to lead gingival inflammation and alveolar bone resorption. Calprotectin levels in gingival crevicular fluid of periodontitis patients are higher than healthy patients. In the present study, the effects of S100A8 and S100A9 on the expressions of pro-inflammatory cytokines and bone metabolism related factor in mouse osteocyte like cells (MLO-Y4-A2) were investigated.
Design: MLO-Y4-A2 cells were treated with S100A8 and S100A9, and the expressions of RAGE, TLR4, RANKL and several inflammatory cytokines were analyzed by PCR and Western blotting or ELISA methods. To investigate the intracellular signaling pathways, phosphorylation of MAPK and STAT3 was determined by Western blotting, and chemical specific inhibitors and siRNAs were used.
Results: Expressions of IL-6 and RANKL were increased by treatment with S100A9 but not S100A8. However, both S100A8 and S100A9 did not changed expression of IL-1β, IL-8 and TNF-α. Although RAGE and TLR4 expressions were not up-regulated by S100A9 treatment, transfection of siRNA for RAGE and TLR4 significantly decreased IL-6 and RANKL expressions. In addition, S100A9 activated p38, ERK and STAT3 signaling pathways, and inhibitors for these factors significantly decreased S100A9 induced IL-6 and RANKL expressions.
Conclusions: These results indicated that S100A9 induces IL-6 and RANKL production via engagement with RAGE and TLR4 signalings in osteocytes and suggested that S100A9 may play important roles in the periodontal alveolar bone destruction.
掲載誌名
BioMed Research International
ISSN
23146133
23146141
出版者
Hindawi
2020
開始ページ
7149408
発行日
2020-02-20
備考
内容要旨・審査要旨・論文本文の公開
内容要旨 : k3380_abstract.pdf
審査要旨 : k3380_review.pdf
論文本文 : k3380_fulltext.pdf (著者最終稿)
論文本文 : bmri_2020_7149408.pdf (雑誌掲載版)
本論文は, 著者Ryosuke Takagiの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
© 2020 Ryosuke Takagi et al. This is an open access article distributed under the Creative Commons Attribution License,( https://creativecommons.org/licenses/by/4.0/ ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3380号
学位記番号
甲口第459号
学位授与年月日
2020-03-23
学位名
博士(歯学)
学位授与機関
徳島大学
部局
病院
歯学系
先端酵素学研究所