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ID 109478
Title Alternative
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.
Author
Shinohara, Hiroki The University of Tokushima
Okamura, Hirohiko The University of Tokushima KAKEN Search Researchers
Yang, Di The University of Tokushima
Keywords
PKR
OSTEOCLAST
RAW264.7
TNF-α
NF-κB
MAPK
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Journal of Cellular Biochemistry
ISSN
07302312
10974644
NCID
AA1052210X
Publisher
Wiley
Volume
116
Issue
9
Start Page
1957
End Page
1967
Published Date
2015-03-04
Remark
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)
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第2857号
Diploma Number
甲口第396号
Granted Date
2015-06-11
Degree Name
Doctor of Dental Science
Grantor
Tokushima University
departments
Oral Sciences