Inflammation ( IF 4.5 ) Pub Date : 2020-05-31 , DOI: 10.1007/s10753-020-01248-3 Yan Gao 1 , Sixiang Wang 1 , Long He 1, 2 , Chunli Wang 1 , Li Yang 1
Osteoarthritis (OA) is a chronic degenerative joint disease which is greatly affected by the inflammatory response triggered by the NF-κB signaling pathway. Alpinetin (APT) is a natural flavonoid compound, which has been reported to have many important biological activities such as antibacterial, antitumor, and anti-inflammatory. However, the action of its effect on chondrocytes in OA has yet to be elucidated. In this study, we investigated APT’s anti-inflammatory action. The effects of APT on cell viability and cytotoxicity of rat chondrocytes was investigated by CCK8. Western blotting, qRT-PCR, and immunofluorescent staining were used to elucidate the molecular mechanisms and signaling pathways of APT mediating anti-inflammatory effects on chondrocytes. An OA model was induced by destabilization of the medial meniscus (DMM) in rats, then APT was injected into the knee articular cavity to examine its anti-inflammatory effects in vivo. These results showed that APT could reduce the TNF-α-induced increase of MMP-13 and ADAMTS-5 and decrease of COL2A1 levels. APT antagonized TNF-α-induced down-regulation of BCL-2 and CDK1. Further studies have shown that APT simultaneously repressed cell nucleus translocation of p65 and the phosphorylation of IκB and activated the phosphorylation of ERK. In vivo, APT suppressed cartilage matrix degradation. In conclusion, APT appears to favorably modulate anti-inflammatory effects in chondrocytes making it a promising compound for OA treatment.
中文翻译:
Alpinetin通过减轻骨关节炎的NF-κB/ ERK途径保护软骨细胞并表现出抗炎作用。
骨关节炎(OA)是一种慢性退行性关节疾病,受NF-κB信号通路触发的炎症反应极大地影响。Alpinetin(APT)是一种天然的类黄酮化合物,据报道具有许多重要的生物学活性,例如抗菌,抗肿瘤和抗炎。然而,其对OA中软骨细胞作用的作用尚未阐明。在这项研究中,我们研究了APT的抗炎作用。通过CCK8研究了APT对大鼠软骨细胞的细胞活力和细胞毒性的影响。Western blotting,qRT-PCR和免疫荧光染色被用于阐明APT介导软骨细胞抗炎作用的分子机制和信号传导途径。大鼠内侧半月板(DMM)失稳,诱发OA模型,体内。这些结果表明,APT可以减少TNF-α诱导的MMP-13和ADAMTS-5的增加以及COL2A1水平的减少。APT拮抗TNF-α诱导的BCL-2和CDK1下调。进一步的研究表明,APT同时抑制p65的细胞核易位和IκB的磷酸化并激活ERK的磷酸化。在体内,APT抑制软骨基质降解。总之,APT似乎可以很好地调节软骨细胞的抗炎作用,使其成为有前景的OA治疗化合物。