論文 - 詳細
| RRC ID | 69756 |
|---|---|
| 著者 | Li R, Guan Z, Bi S, Wang F, He L, Niu X, You Y, Liu Y, Ding Y, Siwko S, Wang N, Zhang Z, Jin Y, Luo J. |
| タイトル | The proton-activated G protein-coupled receptor GPR4 regulates the development of osteoarthritis via modulating CXCL12/CXCR7 signaling. |
| ジャーナル | Cell Death Dis |
| Abstract |
Inflammatory diseases decrease the extracellular environmental pH. However, whether proton-activated G protein-coupled receptors (GPCRs) can regulate the development of osteoarthritis (OA) is largely unknown. In this study, we report that proton-activated GPR4 is essential for OA development. We found a marked increase in expression of the proton-activated GPR4 in human and mouse OA cartilage. Lentivirus-mediated overexpression of GPR4 in mouse joints accelerated the development of OA, including promotion of articular cartilage damage, synovial hyperplasia, and osteophyte formation, while Gpr4 knockout effectively attenuated the development of posttraumatic and aging-associated OA in mice. We also found that inhibition of GPR4 with the antagonist NE52-QQ57 ameliorated OA progression in mice, promoted extracellular matrix (ECM) production, and protected cartilage from degradation in human articular cartilage explants. Moreover, GPR4 overexpression upregulated matrix-degrading enzymes’ expression and inflammation factors under pro-inflammatory and slightly acidic conditions. Mechanistically, GPR4 suppressed chondrocyte differentiation and upregulated cartilage homeostasis through NF-κB/MAPK signaling activation by regulating CXCR7/CXCL12 expression. Together, our results take the lead to illustrate that proton-activated GPCR acts as a key regulator for OA pathogenesis in vivo, and support that GPR4 could be a promising therapeutic target for OA treatment. |
| 巻・号 | 13(2) |
| ページ | 152 |
| 公開日 | 2022-2-14 |
| DOI | 10.1038/s41419-021-04455-4 |
| PII | 10.1038/s41419-021-04455-4 |
| PMID | 35165253 |
| PMC | PMC8844071 |
| MeSH | Animals Cartilage, Articular* / pathology Chemokine CXCL12 / metabolism Chondrocytes / metabolism Mice Osteoarthritis* / metabolism Protons Receptors, CXCR / metabolism Receptors, G-Protein-Coupled* / metabolism Signal Transduction* |
| IF | 6.304 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |