|
|
|
| Exploring the Osteoprotective Effect of Curcumin on Osteoarthritis Model Rats Based on the Ferroptosis Pathway |
| LI Yang, LU Tan, et al |
| The First Affiliated Hospital of Xinxiang Medical University, Henan Xinxiang 453100, China |
|
|
|
|
Abstract Objective: To explore the osteoprotective effect of curcumin on osteoarthritis (OA) model rats based on the ferroptosis pathway. Methods: Chondrocytes were isolated and cultured from 6-8-week-old SD rats.The cells were divided into the control group,the model group (LPS group),the extremely low-dose curcumin group (1μmoL/L),the low-dose curcumin group (10μmoL/L),the medium-dose curcumin group (20μmoL/L),the high-dose curcumin group (40μmoL/L),and the ferroptosis inhibitor ferrostatin-1 (Fer-1) group.Except for the control group,primary chondrocytes in all other groups were treated with lipopolysaccharide (LPS) to establish OA cell models.Cells in the curcumin groups were treated with corresponding doses of curcumin,while cells in the Fer-1 group were treated with 1μM Fer-1.After 48 hours,cell morphology and damage were observed using toluidine blue staining.Cell apoptosis was detected using the TUNEL method.Cell viability was assessed using the CCK-8 assay.The levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were measured using reagent kits.Western blot (WB) was used to detect the protein expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4).Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the mRNA expression levels of GPX4,heat shock protein B1 (HSPB1),and telomere repeat binding factor 1 (TRF1). Results: Compared with the control group,the LPS group showed a reduced number of chondrocytes,damaged cell morphology,smaller cell nuclei,increased apoptosis rate,elevated levels of MDA and ROS,upregulated ACSL4 protein and TRF1 mRNA expression,and decreased cell viability,GPX4 protein,and GPX4 and HSPB1 mRNA expression (P<0.001).Compared with the LPS group,the low-dose,medium-dose,and high-dose curcumin groups and the Fer-1 group exhibited improved chondrocyte injury,reduced apoptosis rate,restored cell viability,decreased levels of MDA,ROS,ACSL4 protein,and TRF1 mRNA expression,and increased GPX4 protein and GPX4 and HSPB1 mRNA expression (P<0.05). Conclusion: Curcumin can effectively reverse LPS-induced damage to OA chondrocytes.The mechanism may be related to improving cellular antioxidant activity,regulating the expression of ferroptosis-related genes (ACSL4,GPX4,HSPB1,and TRF1),and inhibiting chondrocyte ferroptosis.
|
|
|
|
|
|
[1] 殷恺琦,王军威,袁普卫,等.骨关节炎的孟德尔随机化分析研究进展[J].中华骨科杂志,2024,44(10):708-716.
[2] Jiang X,Stockwell BR,Conrad M.Ferroptosis:mechanisms,biology and role in disease[J].Nat Rev Mol Cell Biol,2021,22(4):266-282.
[3] 熊治林,孙红,刘淼,等.铁死亡在椎间盘退变和骨关节炎中的作用[J].中国组织工程研究,2023,27(36):5884-5890.
[4] 陈凡,周富丽,陈勇,等.姜黄素可能通过上调Prdx6蛋白表达抑制软骨细胞铁死亡[J].安徽医科大学学报,2023,58(12):2106-2112.
[5] 桂超,保国锋,崔志明.软骨细胞铁死亡在骨关节炎中的研究进展[J].江苏医药,2022,48(10):1070-1073.
[6] 祖阳.基于累积Meta分析及TSA评价温针灸治疗膝关节骨性关节炎的临床疗效[D].陕西中医药大学,2023.
[7] Chen T,Zhou R,Chen Y,et al.Curcumin ameliorates IL-1β-induced apoptosis by activating autophagy and inhibiting the NF-κB signaling pathway in rat primary articular chondrocytes[J].Cell Biol Int,2021,45(5):976-988.
[8] 廖太阳,张力,丁亮,等.膝痹宁通过CPT1调节大鼠滑膜氧化还原稳态缓解膝骨关节炎疼痛的效应机制[J].解放军医学杂志,2023,48(1):49-57.
[9] Yan Y,He J,Cheng W.Screening of diagnostic biomarkers for ferroptosis-related osteoarthritis and construction of a risk-prognosis model[J].Ann Med Surg (Lond),2024,86(2):856-866.
[10] Ding K,Liu C,Li L,et al.Acyl-CoA synthase ACSL4:an essential target in ferroptosis and fatty acid metabolism[J].Chin Med (Engl),2023,136(21):2521-2537.
[11] 王柯,叶寒露.大黄素对膝骨关节炎大鼠软骨细胞铁死亡的影响及机制研究[J].天津医药,2023,51(10):1090-1097.
[12] 张妍.乳腺癌铁死亡预后模型构建及关键基因HSPB1在乳腺癌耐药转移中的功能及机制研究[D].山东:山东大学,2023.
[13] 孟丽花.PPARα调控TRF及其对铁过载诱发铁死亡的影响机制[D].湖北:华中农业大学,2020.
[14] 牛中科,张翼,王秀霞,等.姜黄素预处理的骨髓间充质干细胞外泌体对骨关节炎软骨细胞的影响[J].中华实验外科杂志,2024,41(2):305-308. |
|
|
|
2025, Vol. 31 
