直近一年間の累計
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ID 115845
著者
Shimo, Tsuyoshi Health Sciences University of Hokkaido
Takebe, Hiroaki Health Sciences University of Hokkaido
Okui, Tatsuo Okayama University
Kunisada, Yuki Okayama University
Ibaragi, Soichiro Okayama University
Obata, Kyoichi Okayama University
Shamsoon, Karnoon University of Hokkaido
Fujii, Saki Health Sciences University of Hokkaido
Hosoya, Akihiro Health Sciences University of Hokkaido
Irie, Kazuharu Health Sciences University of Hokkaido
Sasaki, Akira Okayama University
Iwamoto, Masahiro University of Maryland School of Medicine
キーワード
fracture healing
chondrocyte
interreukin-1β
retinoid signaling
資料タイプ
学術雑誌論文
抄録
The process of fracture healing consists of an inflammatory reaction and cartilage and bone tissue reconstruction. The inflammatory cytokine interleukin-1β (IL-1β) signal is an important major factor in fracture healing, whereas its relevance to retinoid receptor (an RAR inverse agonist, which promotes endochondral bone formation) remains unclear. Herein, we investigated the expressions of IL-1β and retinoic acid receptor gamma (RARγ) in a rat fracture model and the effects of IL-1β in the presence of one of several RAR inverse agonists on chondrocytes. An immunohistochemical analysis revealed that IL-1β and RARγ were expressed in chondrocytes at the fracture site in the rat ribs on day 7 post-fracture. In chondrogenic ATDC5 cells, IL-1β decreases the levels of aggrecan and type II collagen but significantly increased the metalloproteinase-13 (Mmp13) mRNA by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. An RAR inverse agonist (AGN194310) inhibited IL-1β-stimulated Mmp13 and Ccn2 mRNA in a dose-dependent manner. Phosphorylated extracellular signal regulated-kinases (pERK1/2) and p-p38 mitogen-activated protein kinase (MAPK) were increased time-dependently by IL-1β treatment, and the IL-1β-induced p-p38 MAPK was inhibited by AGN194310. Experimental p38 inhibition led to a drop in the IL-1β-stimulated expressions of Mmp13 and Ccn2 mRNA. MMP13, CCN2, and p-p38 MAPK were expressed in hypertrophic chondrocytes near the invaded vascular endothelial cells. As a whole, these results point to role of the IL-1β via p38 MAPK as important signaling in the regulation of the endochondral bone formation in fracture healing, and to the actions of RAR inverse agonists as potentially relevant modulators of this process.
掲載誌名
International Journal of Molecular Sciences
ISSN
14220067
cat書誌ID
AA12038549
出版者
MDPI
21
7
開始ページ
2365
発行日
2020-03-29
権利情報
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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
出版社版
部局
歯学系