杨梅酮通过激活ANXA5/Nrf2/HO-1通路缓解铁死亡相关骨关节炎*

doi:10.3870/j.issn.1672-0741.25.03.022

摘要/Abstract

摘要： 目的探讨杨梅酮治疗骨关节炎(osteoarthritis,OA)的作用机制。方法采用不同浓度的杨梅酮(0、25、50、100、150、200 μmol/L)处理小鼠成软骨细胞ATDC5细胞48 h,采用MTT法检测细胞活力以筛选安全治疗浓度。应用100 ng/mL脂多糖(lipopolysaccharides,LPS)刺激软骨细胞24 h诱导细胞炎症,随后使用50 μmol/L杨梅酮、2.0 μg/mL膜联蛋白A5(ANXA5)过表达载体(pcDNA-ANXA5)以及50 nmol/L ANXA5干扰质粒(si-ANXA5)单独或共同处理ATDC5细胞,采用MTT法以及相关试剂盒检测细胞活力和铁死亡水平。通过交叉韧带横断和内侧半月板切除术构建OA小鼠模型进行体内实验。结果杨梅酮浓度大于100 μmol/L时,ATDC5细胞活力显著降低。杨梅酮可改善LPS诱导的软骨细胞活力的减弱并抑制软骨细胞铁死亡。ANXA5在LPS刺激的ATDC5细胞中低表达。过表达ANXA5通过激活Nrf2/HO-1通路,减弱LPS诱导的ATDC5细胞活力降低和铁死亡的增加。干扰ANXA5可逆转杨梅酮对LPS刺激的ATDC5细胞中铁死亡水平的抑制作用。体内实验进一步证实,杨梅酮通过促进ANXA5表达抑制铁死亡,进而改善OA。结论杨梅酮通过靶向ANXA5激活Nrf2/HO-1通路抑制铁死亡,进而缓解OA,对OA的治疗具有潜在的价值。

关键词: 骨关节炎, 杨梅酮, 膜联蛋白A5, Nrf2/HO-1通路, 铁死亡

Abstract: Objective To explore the mechanism of myricanone (Myri) in the treatment of osteoarthritis(OA). Methods ATDC5 cells were treated with different concentrations of Myri(0,25,50,100,150,200 μmol/L)for 48 h,and the cell viability was detected by MTT to screen the safe therapeutic concentration.ATDC5 cells stimulated with 100 ng/mL lipopolysaccharides(LPS)were used to induce cell inflammation for 24 h,and then ATDC5 cells were treated with 50 μmol/L Myri,2.0 μg/mL annexin A5(ANXA5) overexpression vector(pcDNA-ANXA5)and 50 nmol/L ANXA5 interference plasmid(si-ANXA5)alone or together.Cell viability and ferroptosis levels were detected by MTT and the corresponding commercial kits.The OA mouse model was constructed by cruciate ligament transection and medial meniscectomy for in vivo experiments. Results When the concentration of Myri was more than 100 μmol/L,the activity of ATDC5 cells was decreased.In addition,Myri improved LPS-induced ATDC5 cells viability reduction and inhibited ferroptosis.ANXA5 was lowly expressed in LPS-treated ATDC5 cells.Overexpression of ANXA5 attenuated LPS-induced decrease in ATDC5 cell viability and increase in ferroptosis by activating the Nrf2/HO-1 pathway.Interfering with ANXA5 offset the inhibitory effect of Myri on the level of ferroptosis in LPS-treated ATDC5 cells.In vivoexperiments further confirmed that Myri inhibited ferroptosis by promoting ANXA5 expression,thereby improving OA. Conclusion Myri inhibits ferroptosis and alleviates OA by activating the ANXA5/Nrf2/HO-1 pathway,which may have potential value for the treatment of OA.

Key words: osteoarthritis, myricanone, annexin A5, Nrf2/HO-1 pathway, ferroptosis

中图分类号:

R684.3
R285

马运锋, 韩小飞. 杨梅酮通过激活ANXA5/Nrf2/HO-1通路缓解铁死亡相关骨关节炎^*[J]. 华中科技大学学报（医学版）, 2026, 55(3): 370-377.

Ma Yunfeng, Han Xiaofei. Myricanone Alleviates Ferroptosis-related Osteoarthritis by Activating the ANXA5/Nrf2/HO-1 Pathway[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(3): 370-377.

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杨梅酮通过激活ANXA5/Nrf2/HO-1通路缓解铁死亡相关骨关节炎^*

Myricanone Alleviates Ferroptosis-related Osteoarthritis by Activating the ANXA5/Nrf2/HO-1 Pathway

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