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
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キーワード | fracture healing
chondrocyte
interreukin-1β
retinoid signaling
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資料タイプ |
学術雑誌論文
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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.
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掲載誌名 |
International Journal of Molecular Sciences
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ISSN | 14220067
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cat書誌ID | AA12038549
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出版者 | MDPI
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巻 | 21
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号 | 7
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開始ページ | 2365
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発行日 | 2020-03-29
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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/).
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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
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著者版フラグ |
出版社版
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部局 |
歯学系
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