Curcumin exerts chondroprotective effects against osteoarthritis by promoting AMPK/PINK1/Parkin-mediated mitophagy
Curcumin exerts chondroprotective effects against osteoarthritis by promoting AMPK/PINK1/Parkin-mediated mitophagy
复制标题
姜黄素通过促进 AMPK/PINK1/Parkin 介导的线粒体自噬对骨关节炎发挥软骨保护作用
DOI：
10.1016/j.biopha.2022.113092
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发表时间：
2022-05-10
影响因子：
7.5
通讯作者：
Bai, Lunhao
中科院分区：
文献类型：
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作者：
Jin, Zhuangzhuang;Chang, Bohan;Bai, Lunhao
骨关节炎是一种慢性退行性疾病，具有异质性，发病机制复杂，治疗难度大。姜黄素具有良好的抗炎和抗氧化作用，可能对骨性关节炎具有潜在的治疗价值。在这项研究中，我们研究了姜黄素的作用靶点，并确定了姜黄素潜在的抗OA靶点。基因本体论(GO)和京都基因和基因组百科全书(KEGG)信号通路分析被用来评估这些靶标。此外，我们还建立了单碘乙酸钠诱导的大鼠膝关节骨性关节炎模型和IL-1β诱导的骨性关节炎软骨细胞模型，以验证姜黄素的抗骨关节炎作用及其机制。GO和KEGG分析筛选出七个与代谢过程和AMPK信号通路有关的HUB基因。根据国际骨关节炎研究学会(OARSI)和Mankin对OA大鼠的评分，姜黄素可以显着减弱OA的特征。此外，姜黄素在维持线粒体动态平衡(ROS、Ca~(2+)、ATP产生和线粒体膜电位)方面被显著地用作有丝分裂的激活剂。姜黄素干预后，吞丝相关蛋白的表达水平不仅在关节软骨中增加，在软骨细胞中也有增加。结合验证实验和网络药理学，我们确认了有丝分裂吞噬在姜黄素治疗骨性关节炎中的重要性。姜黄素的软骨保护作用是通过AMPK/PINK1/Parkin途径实现的，姜黄素有望成为治疗骨性关节炎的新药。
Osteoarthritis (OA), a chronic degenerative disease with heterogeneous properties, is difficult to cure due to its complex pathogenesis. Curcumin possesses excellent anti-inflammatory and antioxidant properties and may have potential therapeutic value in OA. In this study, we investigated the action targets of curcumin and identified potential anti-OA targets for curcumin. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses were performed to evaluate these targets. Furthermore, we established a sodium monoiodoacetate-induced rat knee OA model and IL-1 beta induced OA chondrocyte model to verify the effect and mechanism of curcumin against OA. The GO and KEGG analyses screened seven hub genes involved in metabolic processes and the AMPK signaling pathway. Curcumin can significantly attenuate OA characteristics according to Osteoarthritis Research Society International (OARSI) and Mankin scores in OA rats. Additionally, curcumin is notably employed as an activator of mitophagy in maintaining mitochondrial homeostasis (ROS, Ca2+, ATP production, and mitochondrial membrane potential). The expression levels of mitophagy-related proteins were increased not only in articular cartilage but also in chondrocytes with curcumin intervention. Combining validation experiments and network pharmacology, we identified the importance of mitophagy in the curcumin treatment of OA. The chondroprotective effects of curcumin against OA are mediated by the AMPK/ PINK1/Parkin pathway, and curcumin may serve as a potential novel drug for OA management.