Fu Changlong, Lin Yanming, Lin Qing, Lan Shujie, Huang Yanfeng, Tu Haishui, Li Chao, Lu Shiyu, Li Xihai, Zhong Weihong, Ma Dezun
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Fuzhou, Fujian 350122, China; Fujian Provincial Key Laboratory of Integrative Medicine on Geriatrics, Fuzhou, Fujian 350122, China.
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Fuzhou, Fujian 350122, China; Fujian Provincial Key Laboratory of Integrative Medicine on Geriatrics, Fuzhou, Fujian 350122, China.
Biomed Pharmacother. 2024 Dec;181:117597. doi: 10.1016/j.biopha.2024.117597. Epub 2024 Nov 6.
LncRNA XIST and Nav1.7 have been identified to be significantly associated with the onset of osteoarthritis. Prim-O-glucosylcimifugin (POG) has antiinflammatory and analgesic effects in treating osteoarthritis (OA). However, its molecular mechanism of action remains unclear. This research investigated whether POG inhibits OA cartilage degeneration by regulating Nav1.7 through lncRNA XIST. We observed the relationship between lncRNA XIST and Nav1.7 through in vivo and in vitro experiments, and utilized lentiviral plasmids for XIST overexpression to further validate the protective effect of POG against OA. In vivo experiments revealed the close association of improving OA cartilage morphological changes by POG with lncRNA XIST and Nav1.7 downregulation and related proteins expression. In vitro experiments demonstrated significantly up-regulated lncRNA XIST and Nav1.7 expression in IL1β-induced chondrocytes, and their levels and related protein expression decreased after POG intervention. FISH indicated that POG attenuated the fluorescence intensity of lncRNA XIST in chondrocytes. RT-PCR and Western blot assays revealed the positive correlation of lncRNA XIST and Nav1.7 expression in chondrocytes. Additionally, flow cytometry results revealed that POG intervention reduced OA chondrocyte apoptosis. Therefore, we conclude that POG can mediate lncRNA XIST to regulate Nav1.7 to delay cartilage degeneration, which is an effective way to treat OA. However, lncRNA XIST is not the only target for regulation, and further discussion is needed.
长链非编码RNA XIST和Nav1.7已被证实与骨关节炎的发病显著相关。升麻素苷（POG）在治疗骨关节炎（OA）方面具有抗炎和镇痛作用。然而，其分子作用机制尚不清楚。本研究探讨POG是否通过lncRNA XIST调节Nav1.7来抑制OA软骨退变。我们通过体内和体外实验观察lncRNA XIST与Nav1.7之间的关系，并利用慢病毒质粒进行XIST过表达，以进一步验证POG对OA的保护作用。体内实验揭示了POG改善OA软骨形态变化与lncRNA XIST和Nav1.7下调及相关蛋白表达密切相关。体外实验表明，IL1β诱导的软骨细胞中lncRNA XIST和Nav1.7表达显著上调，POG干预后其水平及相关蛋白表达降低。荧光原位杂交表明POG减弱了软骨细胞中lncRNA XIST的荧光强度。逆转录聚合酶链反应和蛋白质免疫印迹分析显示软骨细胞中lncRNA XIST和Nav1.7表达呈正相关。此外，流式细胞术结果显示POG干预减少了OA软骨细胞凋亡。因此，我们得出结论，POG可通过介导lncRNA XIST调节Nav1.7来延缓软骨退变，这是治疗OA的有效途径。然而，lncRNA XIST并非唯一的调控靶点，仍需进一步探讨。
