体内
体外
骨关节炎
软骨
TLR2型
炎症
化学
NF-κB
信号转导
细胞生物学
药理学
生物
生物化学
医学
免疫学
病理
生物技术
解剖
替代医学
TLR4型
作者
Shida Kuang,Zhewen Liu,Lumei Liu,Xinying Fu,Wen S. Sheng,Zongren Hu,Chengxiong Lin,He Qinghu,Jisong Chen,Shuguang Gao
标识
DOI:10.1016/j.ijbiomac.2024.133137
摘要
Polygonatum sibiricum polysaccharides (PSP), the primary constituent of Polygonatum sibiricum, have been shown to exhibit a wide range of pharmacological effects, but their impact on osteoarthritis (OA) remains unclear. The objective of this study was to investigate the protective effects of PSP against OA and to elucidate its underlying molecular mechanism. In our in vitro experiments, PSP not only inhibited the IL-1β-induced inflammatory responses and the nuclear factor kappa-B (NF-κB) signaling pathway in chondrocytes but also regulated the cartilage matrix metabolism. In addition, we detected 394 significantly differentially expressed genes through RNA-seq analysis on PSP-intervened chondrocytes, and the toll-like receptor 2 (TLR2) was identified as the most important feature by functional network analysis and qRT-PCR. It was also revealed that PSP treatment significantly reversed the IL-1-induced up-regulation of TLR2 expression in chondrocytes, while TLR2 overexpression partially inhibited the regulatory effects of PSP on inflammation, NF-κB signaling pathway and matrix metabolism. In our in vivo experiments, PSP treatment alleviated the development of destabilization of medial meniscus (DMM)-induced OA in mouse knee joints, inhibited the DMM-induced activation of the TLR2/NF-κB signaling pathway in mouse knee joint cartilage, and reduced the serum levels of inflammatory cytokines. In conclusion, PSP exerts its anti-inflammatory, matrix synthesis-promoting and matrix catabolism-suppressing effects in knee OA by inhibiting the TLR2/NF-κB signaling pathway, suggesting that PSP may be potentially targeted as a novel all-natural, low-toxicity drug for OA prevention and treatment.
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