中国病理生理杂志2024，Vol.40Issue(7)：1268-1275,8.DOI:10.3969/j.issn.1000-4718.2024.07.015
姜黄素通过调控p53/SLC7A11/GPX4通路抑制脂多糖诱导的RAW264.7源性破骨细胞分化
Curcumin inhibits lipopolysaccharide-induced differentiation of RAW264.7 cell-derived osteoclasts through regulation of p53/SLC7A11/GPX4 pathway
摘要
Abstract
AIM:The study aimed to explore the effect of curcumin(Cur)on lipopolysaccharide(LPS)-in-duced RAW264.7 cell-derived osteoclasts,together with its underlying mechanism.METHODS:An osteoclast model was established by treating RAW264.7 cells with LPS.The viability of the cells was assessed by CCK-8 assays and osteo-clast formation was evaluated by tartrate-resistant acid phosphatase(TRAP)activity.The levels of reactive oxygen species(ROS),Fe2+,glutathione(GSH),and malondialdehyde(MDA)were examined by biochemical assays.Mitochondrial morphology was assessed by transmission electron microscopy.The mRNA and protein levels of p53,glutathione peroxi-dase 4(GPX4),and solute carrier family 7 member 11(SLC7A11)were determined by RT-qPCR and Western blot,re-spectively.RESULTS:Treatment with LPS successfully induced osteoclasts formation in RAW264.7 cells.The TRAP results showed that compared with the LPS-treated group,the number of osteoclasts and TRAP activity in the curcumin-treated group decreased dose-dependently(P<0.01).Compared with the control group,the LPS+Erastin group showed significantly increased TRAP activity(P<0.01),while after curcumin treatment,the TRAP activity declined in a dose-de-pendent manner(P<0.01).The results of the biochemical tests showed that compared with the control group,the LPS+Erastin group had significantly elevated levels of ROS,Fe2+,and MDA,while the GSH level was significantly reduced(P<0.01),and compared with the LPS+Erastin group,the ROS,Fe2+,and MDA levels in the curcumin group decreased(P<0.01)and GSH levels increased(P<0.01).These effects were all dose-dependent.Transmission electron microscopy showed that compared with the LPS group,the LPS+Erastin group had reduced mitochondrial cristae and increased mem-brane density,while after treatment with curcumin,both these effects were reversed.The RT-qPCR and Western blot re-sults showed that compared with the control group,the mRNA and protein levels of p53 in the LPS+Erastin group were sig-nificantly increased,while those of of SLC7A11 and GPX4 were significantly reduced(P<0.01).After curcumin treat-ment,the p53 mRNA and protein levels were reduced while the levels of SLC7A11 and GPX4 were increased(P<0.01).CONCLUSION:Curcumin can inhibit lipopolysaccharide-induced differentiation of RAW264.7 cells into osteoclasts,and its mechanism may be related to the inhibition of the p53/SLC7A11/GPX4 signaling pathway.关键词
骨质疏松/铁死亡/破骨细胞/p53/SLC7A11/GPX4信号通路/姜黄素Key words
osteoporosis/ferroptosis/osteoclast/p53/SLC7A11/GPX4 signaling pathway/curcumin分类
医药卫生引用本文复制引用
李明,陈宗海,朱青,颜丽君,张宗星,邹权,陈龙菊..姜黄素通过调控p53/SLC7A11/GPX4通路抑制脂多糖诱导的RAW264.7源性破骨细胞分化[J].中国病理生理杂志,2024,40(7):1268-1275,8.基金项目
国家自然科学基金资助项目(No.81260192) （No.81260192）
风湿性疾病发生与干预湖北省重点实验室第四批开放基金项目(No.OIR19007A) （No.OIR19007A）
湖北民族大学研究生教育创新项目(No.MYK2024004) （No.MYK2024004）
