ID 109478
タイトル別表記
二本鎖RNA依存性プロテインキナーゼは in vitroとin vivo においてTNF-αによる破骨細胞形成に必要である
PKR is necessary for osteoclastogenesis.
著者
篠原, 宏貴 徳島大学大学院口腔科学教育部(口腔科学専攻)
岡村, 裕彦 The University of Tokushima KAKEN研究者をさがす
楊, 諦 The University of Tokushima
キーワード
PKR
OSTEOCLAST
RAW264.7
TNF-α
NF-κB
MAPK
資料タイプ
学位論文
抄録
Double-stranded RNA-dependent protein kinase (PKR) is involved in cell cycle progression, cell proliferation, cell differentiation, tumorgenesis, and apoptosis. We previously reported that PKR is required for differentiation and calcification in osteoblasts. TNF-α plays a key role in osteoclast differentiation. However, it is unknown about the roles of PKR in the TNF-α-induced osteoclast differentiation. The expression of PKR in osteoclast precursor RAW264.7 cells increased during TNF-α-induced osteoclastogenesis. The TNF-α-induced osteoclast differentiation in bone marrow-derived macrophages and RAW264.7 cells was markedly suppressed by the pre-treatment of PKR inhibitor, 2-aminopurine (2AP), as well as gene silencing of PKR. The expression of gene markers in the differentiated osteoclasts including TRAP, Calcitonin receptor, cathepsin K and ATP6V0d2 was also suppressed by the 2AP treatment. Bone resorption activity of TNF-α-induced osteoclasts was also supressed by 2AP treatment. Inhibition of PKR supressed the TNF-α-induced activation of NF-κB and MAPK in RAW264.7 cells. 2AP inhibited both the nuclear translocation of NF-κB and its transcriptional activity in RAW264.7 cells. 2AP inhibited the TNF-α-induced expression of NFATc1 and c-fos, master transcription factors in osteoclastogenesis. TNF-α-induced nuclear translocation of NFATc1 in mature osteoclasts was clearly inhibited by the 2AP treatment. The PKR inhibitor C16 decreased the TNF-α-induced osteoclast formation and bone resorption in mouse calvaria. The present study indicates that PKR is necessary for the TNF-α-induced osteoclast differentiation in vitro and in vivo.
掲載誌名
Journal of Cellular Biochemistry
ISSN
07302312
10974644
cat書誌ID
AA1052210X
出版者
Wiley
116
9
開始ページ
1957
終了ページ
1967
発行日
2015-03-04
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨 : LID201507171001.pdf
審査要旨 : LID201507171002.pdf
論文本文 : k2857_fulltext.pdf
本論文は,著者Hiroki Shinohara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。
著者の申請により要約(2015-07-18公開)に替えて論文全文を公開(2019-09-26)
権利情報
This is the peer reviewed version of the following article: Shinohara, H. , Teramachi, J. , Okamura, H. , Yang, D. , Nagata, T. and Haneji, T. (2015), Double Stranded RNA‐Dependent Protein Kinase is Necessary for TNF‐α‐Induced Osteoclast Formation In Vitro and In Vivo. J. Cell. Biochem., 116: 1957-1967, which has been published in final form at https://doi:10.1002/jcb.25151. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
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2857号
学位記番号
甲口第396号
学位授与年月日
2015-06-11
学位名
博士(歯学)
学位授与機関
徳島大学
部局
歯学系