南方医科大学学报2025，Vol.45Issue(12)：2541-2550,10.DOI:10.12122/j.issn.1673-4254.2025.12.02
巴戟天多糖通过靶向lncRNA XIST调控糖酵解-焦亡延缓小鼠骨关节炎软骨细胞退变
Morinda officinalis polysaccharide delays osteoarthritis mouse chondrocyte degeneration by modulating the glycolysis-pyroptosis axis via targeting the lncRNA XIST
摘要
Abstract
Objective To investigate the mechanism by which Morinda officinalis polysaccharide(MOP)delays osteoarthritis chondrocyte degeneration.Methods In primary cultures of chondrocytes from 4-week-old C57BL/6 mice,the effects of IL-1β and MOP treatment at different concentrations on cell viability were assessed with CCK-8 assay.The treated cells were examined for protein expressions of PKM2,caspase-1,and GSDMD using Western blotting and for XIST expression using fluorescence in situ hybridization(FISH).In IL-1β-induced mouse chondrocytes,the effects of MOP,transfection for XIST overexpression or knockdown,and MOP treatment after the transfection were tested by detecting mRNA levels of GluT1,HK2,PKM2,LDHA,PFKFB3,NLRP3,caspase-1,and GSDMD;flow cytometry,Western blotting,and toluidine blue staining were used to analyze chondrocyte apoptosis,expressions of glycolysis and pyroptosis regulators,and glycosaminoglycan expression.Results The second-passage chondrocytes showed good viability and positive collagen II staining.IL-1β induction caused degenerative morphological changes of the cells,decreased collagen II expression,and upregulated cellular expressions of PKM2,caspase-1,and GSDMD proteins.MOP treatment(especially at 4 mg/mL)significantly enhanced cell viability and reduced HK2,PKM2,caspase-1 and GSDMD expressions in IL-1β-induced mouse chondrocytes.XIST was localized predominantly in the nuclei of the chondrocytes,and its expression increased significantly in IL-1β-treated cells,and was attenuated by MOP treatment.XIST overexpression synergized with IL-1β to upregulate mRNA and protein expressions of glycolysis-and pyroptosis-related factors in the chondrocytes,and such effects were obviously attenuated by MOP.Conversely,XIST knockdown significantly inhibited chondrocyte apoptosis and glycosaminoglycan expression,and down-regulated glycolysis-and pyroptosis-related proteins.MOP treatment exhibited similar protective effects to XIST knockdown,and their combination significantly augmented these protective effects.Conclusions MOP mitigates IL-1β-induced mouse chondrocyte degeneration by modulating glycolysis and pyroptosis via targeting XIST.关键词
巴戟天多糖/骨关节炎/退变软骨细胞/细胞焦亡/糖酵解/lncRNA XISTKey words
Morinda officinalis polysaccharide/osteoarthritis/degenerated chondrocytes/pyroptosis/glycolysis/lncRNA XIST引用本文复制引用
FU Changlong,CHEN Ruolan,XU Shiqi,YOU Jinxin,LIN Qing,HUANG Yanfeng..巴戟天多糖通过靶向lncRNA XIST调控糖酵解-焦亡延缓小鼠骨关节炎软骨细胞退变[J].南方医科大学学报,2025,45(12):2541-2550,10.基金项目
国家自然科学基金(82474532) （82474532）
福建省中青年教师教育科研项目(JAT231042) （JAT231042）
福建省自然科学基金(2024J01138) （2024J01138）
福建中医药大学校管课题(X2023024)Supported by National Natural Science Foundation of China(82474532). （X2023024）
