Zhang Zhiguo, Fu Fangda, Bian Yishan, Zhang Huihao, Yao Sai, Zhou Chengcong, Ge Yuying, Luo Huan, Chen Yuying, Ji Weifeng, Tian Kun, Yue Ming, Du Weibin, Jin Hongting, Tong Peijian, Wu Chengliang, Ruan Hongfeng
Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, People's Republic of China.
The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
J Inflamm Res. 2022 Oct 17;15:5873-5888. doi: 10.2147/JIR.S382675. eCollection 2022.
BACKGROUND: With the rapid growth of the elderly population, the incidence of osteoarthritis (OA) increases annually, which has attracted extensive attention in public health. The roles of dietary intake in controlling joint disorders are perhaps one of the most frequently posed questions by OA patients, while the information about the interaction between dietary intake and OA based on scientific research is limited. α-Chaconine is the richest glycoalkaloid in eggplants such as potatoes. Previous evidence suggests that -Chaconine is a toxic compound to nervous and digestive systems with potentially severe and fatal consequences for humans and farm animals, but its effect on OA development remains obscure. OBJECTIVE: To determine whether -Chaconine deteriorates OA progression through sensory innervation and chondrocyte pyroptosis via regulating nuclear factor-κB (NF-κB) signaling, providing evidence for a possible linkage between -Chaconine and OA progression. METHODS: We established a mouse OA model by destabilization of medial meniscus (DMM) surgery and then intra-articular injection of 20 or 100 μM -Chaconine into the OA mice for 8 and 12 weeks. The severity of OA progression was evaluated by histological staining and radiographic analyses. The expressions of matrix metabolic indicators, Col2, Mmp3, and Mmp13, as well as pyroptosis-related proteins, Nlrp3, Caspase-1, Gsdmd, IL-1β, IL-18, were determined by immunohistochemistry. And the changes in sensory nerve ingrowth and activity of NF-κB signaling were determined by immunofluorescence. RESULTS: We found that -Chaconine could exacerbate mouse OA progression, resulting in subchondral sclerosis, osteophyte formation, and higher OARSI scores. Specifically, -Chaconine could augment cartilage matrix degradation and induce chondrocyte pyroptosis and nerve ingrowth. Mechanistical analysis revealed that -Chaconine stimulated NF-κB signaling by promoting I-κB phosphorylation and p65 nuclear translocation. CONCLUSION: Collectively, our findings raise the possibility that -Chaconine intake can boost chondrocyte pyroptosis and nerve ingrowth to potentiate OA progression by activating NF-κB signaling.
背景：随着老年人口的快速增长，骨关节炎（OA）的发病率逐年上升，这在公共卫生领域引起了广泛关注。饮食摄入在控制关节疾病中的作用可能是OA患者最常提出的问题之一，而基于科学研究的饮食摄入与OA之间相互作用的信息有限。α-查茄碱是土豆等茄子中含量最丰富的糖苷生物碱。先前的证据表明，α-查茄碱是一种对神经和消化系统有毒的化合物，对人类和农场动物可能产生严重和致命的后果，但其对OA发展的影响仍不清楚。 目的：通过调节核因子-κB（NF-κB）信号通路，确定α-查茄碱是否通过感觉神经支配和软骨细胞焦亡加剧OA进展，为α-查茄碱与OA进展之间的可能联系提供证据。 方法：我们通过内侧半月板不稳定（DMM）手术建立小鼠OA模型，然后向OA小鼠关节腔内注射20或100μMα-查茄碱，持续8周和12周。通过组织学染色和影像学分析评估OA进展的严重程度。通过免疫组织化学测定基质代谢指标、Col2、Mmp3和Mmp13以及焦亡相关蛋白Nlrp3、Caspase-1、Gsdmd、IL-1β、IL-18的表达。通过免疫荧光测定感觉神经向内生长和NF-κB信号通路活性的变化。 结果：我们发现α-查茄碱会加剧小鼠OA进展，导致软骨下硬化、骨赘形成和更高的OARSI评分。具体而言，α-查茄碱会增加软骨基质降解，诱导软骨细胞焦亡和神经向内生长。机制分析表明，α-查茄碱通过促进I-κB磷酸化和p65核转位来刺激NF-κB信号通路。 结论：总体而言，我们的研究结果提出了一种可能性，即摄入α-查茄碱可通过激活NF-κB信号通路促进软骨细胞焦亡和神经向内生长，从而增强OA进展。
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