論文 - 詳細
| RRC ID | 54738 |
|---|---|
| 著者 | Pirozzi C, Francisco V, Guida FD, Gómez R, Lago F, Pino J, Meli R, Gualillo O. |
| タイトル | Butyrate Modulates Inflammation in Chondrocytes via GPR43 Receptor. |
| ジャーナル | Cell Physiol Biochem |
| Abstract |
BACKGROUND/AIMS:Osteoarthritis (OA) is a joint degenerative biomechanical disorder involving immunity, metabolic alterations, inflammation, and cartilage degradation, where chondrocytes play a pivotal role. OA has not effective pharmacological treatments and new therapeutic targets are needed. Adipokines contribute to the low-grade systemic inflammation in OA. Here, we explored novel molecular mechanisms of sodium butyrate (BuNa) in modulating inflammation and chemotaxis in chondrocytes, demonstrating the direct involvement of its G protein-coupled receptor (GPR)-43. METHODS:ATDC5 murine chondrocytes were stimulated with interleukin (IL)-1β, in the presence or not of BuNa, for 24 h. RT-PCR and Western blot analysis was performed to evaluate the expression of inflammatory mediators and structural proteins. RESULTS:Butyrate reduced the expression of canonic pro-inflammatory mediators (Nos2, COX-2, IL-6), pro-inflammatory adipokines (lipocalin-2 and nesfatin-1) and adhesion molecule (VCAM-1 and ICAM-1) in IL-1β-stimulated chondrocytes, inhibiting several inflammatory signalling pathways (NFκB, MAPKinase, AMPK-α, PI3K/Akt). Butyrate also reduced metalloproteinase production and limited the loss of type II collagen in IL-1β-inflamed chondrocytes. The chemoattractant effect of butyrate, after different inflammatory challenges, was revealed by increased annexin (AnxA)1 levels and chemokines expression. The chemoattractant and anti-inflammatory activities of butyrate were completely blunted by GPR43 silencing using RNA interference. CONCLUSION:Taken together, our data suggest the potential application of sodium butyrate as a novel candidate in a multi-target approach for the treatment of chondrocyte inflammation and cartilage degenerative process. |
| 巻・号 | 51(1) |
| ページ | 228-243 |
| 公開日 | 2018-11-16 |
| DOI | 10.1159/000495203 |
| PII | 000495203 |
| PMID | 30448827 |
| MeSH | Adipokines / metabolism Animals Annexin A1 / metabolism Butyric Acid / pharmacology* Cell Adhesion Molecules / metabolism Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / metabolism Collagen Type II / genetics Collagen Type II / metabolism Cyclooxygenase 2 / metabolism Inflammation Mediators / metabolism Interleukin-1beta / pharmacology Matrix Metalloproteinase 13 / genetics Matrix Metalloproteinase 13 / metabolism Mice NF-kappa B / metabolism Nitric Oxide Synthase Type II / genetics Nitric Oxide Synthase Type II / metabolism RNA Interference RNA, Small Interfering / metabolism Receptors, G-Protein-Coupled / antagonists & inhibitors Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / metabolism* Signal Transduction / drug effects* |
| IF | 5.5 |
| 引用数 | 8 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |