| RRC ID |
74832
|
| 著者 |
Shimo T, Takebe H, Okui T, Kunisada Y, Ibaragi S, Obata K, Kurio N, Shamsoon K, Fujii S, Hosoya A, Irie K, Sasaki A, Iwamoto M.
|
| タイトル |
Expression and Role of IL-1β Signaling in Chondrocytes Associated with Retinoid Signaling during Fracture Healing.
|
| ジャーナル |
Int J Mol Sci
|
| Abstract |
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.
|
| 巻・号 |
21(7)
|
| 公開日 |
2020-3-29
|
| DOI |
10.3390/ijms21072365
|
| PII |
ijms21072365
|
| PMID |
32235405
|
| PMC |
PMC7177407
|
| MeSH |
Animals
Biomarkers
Chondrocytes / drug effects*
Chondrocytes / metabolism*
Fracture Healing / drug effects*
Fracture Healing / genetics
Gene Expression
Immunohistochemistry
Interleukin-1beta / metabolism*
Male
Mice
Mitogen-Activated Protein Kinases / metabolism
Models, Biological
Protein Transport
Rats
Receptors, Retinoic Acid / agonists
Receptors, Retinoic Acid / genetics
Receptors, Retinoic Acid / metabolism
Retinoids / pharmacology*
Signal Transduction / drug effects*
|
| IF |
4.556
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
