[1]汤样华,杜伟斌,周蒙能,等.β-蜕皮甾酮干预白细胞介素-1β诱导的骨关节炎软骨细胞的效果及其作用机制研究[J].中医正骨,2026,38(01):7-16.
　TANG Yanghua,DU Weibin,ZHOU Mengneng,et al.Effect and mechanism of β-ecdysterone on interleukin-1β-induced osteoarthritis chondrocytes[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2026,38(01):7-16.
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β-蜕皮甾酮干预白细胞介素-1β诱导的骨关节炎软骨细胞的效果及其作用机制研究()

《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第38卷
期数:
2026年01期
页码:
7-16
栏目:
基础研究
出版日期:
2026-01-20

文章信息/Info

Title:
Effect and mechanism of β-ecdysterone on interleukin-1β-induced osteoarthritis chondrocytes
作者:
汤样华1; 杜伟斌1; 周蒙能2; 熊振飞1; 李国松1
1.杭州市萧山区中医院,浙江 杭州 311201; 2.浙江中医药大学第三临床医学院,浙江 杭州 310053
Author(s):
TANG Yanghua1; DU Weibin1; ZHOU Mengneng2; XIONG Zhenfei1; LI Guosong1
1.Xiaoshan Hospital of Traditional Chinese Medicine,Hangzhou 311201,Zhejiang,China; 2.The Third Clinical Medical College of Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang,China
关键词:
骨关节炎;  软骨细胞;  大鼠;  白细胞介素-1β;  蜕皮甾酮;  低氧诱导因子-1α;  血管内皮生长因子;  实验研究
Keywords:
osteoarthritis;  chondrocytes;  rats;  interleukin-1beta;  ecdysterone;  hypoxia-inducible factor-1α;  vascular endothelial growth factors;  experimental study
摘要:
目的:探讨β-蜕皮甾酮干预白细胞介素(interleukin,IL)-1β诱导的骨关节炎(osteoarthritis,OA)软骨细胞的效果及其作用机制。方法:①β-蜕皮甾酮干预浓度筛选。取处于对数生长期的大鼠软骨细胞,分为对照组、20 μmol·L-1β-蜕皮甾酮组、40 μmol·L-1β-蜕皮甾酮组、60 μmol·L-1β-蜕皮甾酮组、80 μmol·L-1β-蜕皮甾酮组、100 μmol·L-1β-蜕皮甾酮组; 除对照组外,其余各组软骨细胞分别采用20、40、60、80、100 μmol·L-1的β-蜕皮甾酮干预24 h,采用CCK-8法检测各组软骨细胞活力。②β-蜕皮甾酮干预IL-1β诱导的OA软骨细胞的效果及作用机制分析。取处于对数生长期的大鼠软骨细胞,分为空白对照组、模型组、20 μmol·L-1β-蜕皮甾酮组、40 μmol·L-1β-蜕皮甾酮组。除空白对照组外,其余各组软骨细胞培养基中均加入终浓度为10 ng·mL-1的IL-1β,同时20 μmol·L-1β-蜕皮甾酮组、40 μmol·L-1β-蜕皮甾酮组软骨细胞培养基中分别加入终浓度为20、40 μmol·L-1的β-蜕皮甾酮,孵育24 h。采用CCK-8法检测各组软骨细胞活力,采用原位末端转移酶标记法检测各组软骨细胞凋亡率,采用实时定量PCR检测各组软骨细胞中基质金属蛋白酶(matrix metalloproteinase,MMP)-13和Ⅱ型胶原蛋白α1链(collagen Ⅱα1,COL2A1)的mRNA表达水平,采用Western Blot法检测软骨细胞中低氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的蛋白表达水平。③软骨细胞HIF-1α mRNA过表达体系验证。取处于对数生长期的软骨细胞,分为空白对照组、HIF-1α过表达组和HIF-1α过表达阴性对照组,HIF-1α过表达组和HIF-1α过表达阴性对照组分别采用含HIF-1α过表达质粒的脂质体2000和含空质粒的脂质体2000转染大鼠软骨细胞,采用实时定量PCR检测各组软骨细胞中HIF-1α的mRNA表达水平。④β-蜕皮甾酮干预IL-1β诱导的OA软骨细胞的作用机制验证。取处于对数生长期的大鼠软骨细胞,分为空白对照组、模型组、40 μmol·L-1β-蜕皮甾酮组、HIF-1α过表达组和HIF-1α过表达阴性对照组。分别采用含HIF-1α过表达质粒的脂质体2000和含空质粒的脂质体2000转染HIF-1α过表达组和HIF-1α过表达阴性对照组软骨细胞; 除空白对照组外,其余各组软骨细胞培养基中均加入终浓度为10 ng·mL-1的IL-1β,同时40 μmol·L-1β-蜕皮甾酮组、HIF-1α过表达组和HIF-1α过表达阴性对照组软骨细胞培养基中均加入终浓度为40 μmol·L-1的β-蜕皮甾酮,孵育24 h。采用②中相应的方法检测各组软骨细胞活力、凋亡率、MMP-13和COL2A1的mRNA表达水平及VEGF的蛋白表达水平。结果:①β-蜕皮甾酮干预浓度筛选结果。20 μmol·L-1β-蜕皮甾酮组、40 μmol·L-1β-蜕皮甾酮组软骨细胞活力与对照组的差异均无统计学意义(P=0.993,P=0.753),60 μmol·L-1β-蜕皮甾酮组、80 μmol·L-1β-蜕皮甾酮组、100 μmol·L-1β-蜕皮甾酮组软骨细胞活力均小于对照组(P=0.000,P=0.000,P=0.000)。确定将20 μmol·L-1和40 μmol·L-1作为β-蜕皮甾酮的干预浓度。②β-蜕皮甾酮干预IL-1β诱导的OA软骨细胞的效果及作用机制分析结果。模型组软骨细胞活力低于空白对照组(P=0.000),凋亡率高于空白对照组(P=0.000); 20 μmol·L-1β-蜕皮甾酮组、40 μmol·L-1β-蜕皮甾酮组软骨细胞活力均高于模型组(P=0.012,P=0.000),凋亡率均低于模型组(P=0.000,P=0.000)。模型组软骨细胞中MMP-13的mRNA相对表达量高于空白对照组(P=0.000),COL2A1的mRNA相对表达量低于空白对照组(P=0.000); 20 μmol·L-1β-蜕皮甾酮组、40 μmol·L-1β-蜕皮甾酮组软骨细胞中MMP-13的mRNA相对表达量均低于模型组(P=0.021,P=0.000),COL2A1的mRNA相对表达量均高于模型组(P=0.000,P=0.000); 40 μmol·L-1β-蜕皮甾酮组软骨细胞中MMP-13的mRNA相对表达量与20 μmol·L-1β-蜕皮甾酮组的差异无统计学意义(P=0.257),COL2A1的mRNA相对表达量高于20 μmol·L-1β-蜕皮甾酮组(P=0.016)。模型组软骨细胞中HIF-1α、VEGF的蛋白相对表达量均高于空白对照组(P=0.000,P=0.000); 20 μmol·L-1β-蜕皮甾酮组软骨细胞中HIF-1α的蛋白相对表达量与模型组的差异无统计学意义(P=0.067),VEGF的蛋白相对表达量低于模型组(P=0.000); 40 μmol·L-1β-蜕皮甾酮组软骨细胞中HIF-1α、VEGF的蛋白相对表达量均低于模型组和20 μmol·L-1β-蜕皮甾酮组(P=0.000,P=0.000; P=0.002,P=0.000)。③软骨细胞HIF-1α mRNA过表达体系验证结果。HIF-1α过表达组软骨细胞中HIF-1α的mRNA相对表达量高于空白对照组和HIF-1α过表达阴性对照组(P=0.000,P=0.000),HIF-1α过表达阴性对照组软骨细胞中HIF-1α的mRNA相对表达量与空白对照组的差异无统计学意义(P=0.773)。④β-蜕皮甾酮干预IL-1β诱导的OA软骨细胞的作用机制验证结果。模型组软骨细胞活力低于空白对照组(P=0.000),凋亡率高于空白对照组(P=0.000); 40 μmol·L-1β-蜕皮甾酮组和HIF-1α过表达阴性对照组软骨细胞活力均高于模型组(P=0.000,P=0.000),凋亡率均低于模型组(P=0.007,P=0.010); 40 μmol·L-1β-蜕皮甾酮组软骨细胞活力、凋亡率与HIF-1α过表达阴性对照组的差异均无统计学意义(P=0.999,P=0.999),HIF-1α过表达组软骨细胞活力、凋亡率与模型组的差异均无统计学意义(P=0.999,P=0.458)。模型组软骨细胞中MMP-13的mRNA相对表达量高于空白对照组(P=0.000),COL2A1的mRNA相对表达量低于空白对照组(P=0.000); 40 μmol·L-1β-蜕皮甾酮组和HIF-1α过表达阴性对照组软骨细胞中MMP-13的mRNA相对表达量均低于模型组(P=0.000,P=0.000),COL2A1的mRNA相对表达量均高于模型组(P=0.000,P=0.000); 40 μmol·L-1β-蜕皮甾酮组软骨细胞中MMP-13和COL2A1的mRNA相对表达量与HIF-1α过表达阴性对照组的差异均无统计学意义(P=0.993,P=0.999); HIF-1α过表达组软骨细胞中MMP-13的mRNA相对表达量与模型组的差异无统计学意义(P=0.121),COL2A1的mRNA相对表达量高于模型组(P=0.043)。模型组软骨细胞中VEGF的蛋白相对表达量低于空白对照组(P=0.000),40 μmol·L-1β-蜕皮甾酮组和HIF-1α过表达阴性对照组软骨细胞中VEGF的蛋白相对表达量均低于模型组(P=0.000,P=0.000),40 μmol·L-1β-蜕皮甾酮组软骨细胞中VEGF的蛋白相对表达量与HIF-1α过表达阴性对照组的差异无统计学意义(P=0.996),HIF-1α过表达组软骨细胞中VEGF的蛋白相对表达量高于模型组(P=0.000)。结论:β-蜕皮甾酮能够增强IL-1β诱导的OA软骨细胞的活力,抑制其凋亡,其作用机制与抑制HIF-1α-VEGF信号通路的激活密切相关。
Abstract:
Objective:To investigate the effect of β-ecdysterone on interleukin(IL)-1β-induced osteoarthritis(OA)chondrocytes and its mechanism.Methods:①Screening of intervention concentration of β-ecdysterone.Chondrocytes of rats in logarithmic growth phase were divided into control group and β-ecdysterone groups with concentrations of 20,40,60,80 and 100 μmol·L-1, respectively.Except for the control group,the chondrocytes in the other groups were treated with 20,40,60,80 and 100 μmol·L-1 β-ecdysterone for 24 hours,and the viability of chondrocytes in each group was detected by CCK-8 method.②Analysis of effect and mechanism of β-ecdysterone on IL-1β-induced OA chondrocytes.The rat chondrocytes in logarithmic growth phase were divided into blank control group,model group,20 μmol·L-1 β-ecdysterone group and 40 μmol·L-1 β-ecdysterone group.Except for the blank control group,IL-1β with a final concentration of 10 ng·mL-1 was added to the chondrocyte culture medium of the other groups.At the same time,β-ecdysterone with a final concentration of 20 and 40 μmol·L-1 was added to the chondrocyte culture medium of the 20 μmol·L-1 β-ecdysterone group and the 40 μmol·L-1 β-ecdysterone group,respectively,and incubated for 24 hours.The viability of chondrocytes in each group was detected using CCK-8 method.The apoptosis rate of chondrocytes in each group was evaluated using TUNEL assay.The mRNA expression levels of matrix metalloproteinase(MMP)-13 and collagenⅡα1(COL2A1)in chondrocytes of each group were detected by real-time quantitative PCR.The protein expression levels of hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)in chondrocytes were detected by Western Blot.③Verification of HIF-1α mRNA overexpression system in chondrocytes.Chondrocytes in logarithmic growth phase were divided into blank control group,HIF-1α overexpression group and HIF-1α overexpression negative control group.HIF-1α overexpression group and HIF-1α overexpression negative control group were transfected into rat chondrocytes with liposome 2000 containing HIF-1α overexpression plasmid and liposome 2000 containing empty plasmid,respectively.The mRNA expression level of HIF-1α in chondrocytes of each group was detected by real-time quantitative PCR.④Verification of the mechanism of β-ecdysterone in interventing IL-1β-induced OA chondrocytes.Rat chondrocytes in logarithmic growth phase were divided into blank control group,model group,40 μmol·L-1 β-ecdysterone group,HIF-1α overexpression group and HIF-1α overexpression negative control group.Chondrocytes of HIF-1α overexpression group and HIF-1α overexpression negative control group were transfected with liposome 2000 containing HIF-1α overexpression plasmid and empty plasmid,respectively.Except for the blank control group,IL-1β with a final concentration of 10 ng·mL-1 was added to the chondrocyte culture medium of the other groups.At the same time,β-ecdysterone with a final concentration of 40 μmol·L-1 was added to the chondrocyte culture medium of the 40 μmol·L-1 β-ecdysterone group,HIF-1α overexpression group and HIF-1α overexpression negative control group,and incubated for 24 hours.Chondrocyte viability,apoptosis rate,mRNA expression levels of MMP-13 and COL2A1,and protein expression levels of VEGF in each group were assessed using the methods described in Part 2.Results:①Screening results of intervention concentration of β-ecdysterone.There was no significant difference in chondrocyte viability between 20 μmol·L-1 β-ecdysterone group and control group(P=0.993),and between 40 μmol·L-1 β-ecdysterone group and control group(P=0.753).The chondrocyte viability of 60,80 and 100 μmol·L-1 β-ecdysterone groups was lower than that of control group(P=0.000,P=0.000,P=0.000).The concentrations of 20 and 40 μmol·L-1 were determined as the intervention concentration of β-ecdysterone.②The analysis result of effect and mechanism of β-ecdysterone on IL-1β-induced OA chondrocytes.The viability of chondrocytes in the model group was lower than that in the blank control group(P=0.000),and the apoptosis rate was higher than that in the blank control group(P=0.000).The viability of chondrocytes in the 20 and 40 μmol·L-1 β-ecdysterone groups was higher than that in the model group(P=0.012,P=0.000),and the apoptosis rate was lower than that in the model group(P=0.000,P=0.000).The relative expression level of MMP-13 mRNA in chondrocytes of the model group was higher than that of the blank control group(P=0.000),and the relative expression level of COL2A1 mRNA was lower than that of the blank control group(P=0.000).The relative expression level of MMP-13 mRNA in chondrocytes of the 20 and 40 μmol·L-1 β-ecdysterone groups was lower than that of the model group(P=0.021,P=0.000),and the relative expression level of COL2A1 mRNA was higher than that in the model group(P=0.000,P=0.000).There was no significant difference in the relative expression level of MMP-13 mRNA between the 40 μmol·L-1 β-ecdysterone group and the 20 μmol·L-1 β-ecdysterone group(P=0.257).The relative mRNA expression level of COL2A1 was higher than that of the 20 μmol·L-1 β-ecdysterone group(P=0.016).The relative expression levels of HIF-1α and VEGF in chondrocytes of the model group were higher than that of the blank control group(P=0.000,P=0.000).There was no significant difference in the relative expression level of HIF-1α protein in chondrocytes between the 20 μmol·L-1 β-ecdysterone group and the model group(P=0.067),while the relative expression level of VEGF protein was lower than that in the model group(P=0.000).The relative expression levels of HIF-1α protein and VEGF protein in chondrocytes of 40 μmol·L-1 β-ecdysterone group were lower than those of model group and 20 μmol·L-1 β-ecdysterone group(P=0.000,P=0.000,P=0.002,P=0.000).③The verification results of HIF-1α mRNA overexpression system in chondrocytes.The relative expression level of HIF-1α mRNA in chondrocytes of HIF-1α overexpression group was higher than that in blank control group and HIF-1α overexpression negative control group(P=0.000,P=0.000).There was no significant difference in the relative expression level of HIF-1α mRNA between HIF-1α overexpression negative control group and blank control group(P=0.773).④The verification results of the mechanism of β-ecdysterone on IL-1β-induced OA chondrocytes.The viability of chondrocytes in the model group was lower than that in the blank control group(P=0.000),and the apoptosis rate was higher than that in the blank control group(P=0.000).The viability of chondrocytes in 40 μmol·L-1 β-ecdysterone group and HIF-1α overexpression negative control group was higher than that in model group(P=0.000,P=0.000),and the apoptosis rate was lower than that in model group(P=0.007,P=0.010).There was no significant difference in chondrocyte viability and apoptosis rate between 40 μmol·L-1 β-ecdysterone group and HIF-1α overexpression negative control group(P=0.999,P=0.999).There was no significant difference in chondrocyte viability and apoptosis rate between HIF-1α overexpression group and model group(P=0.999,P=0.458).The relative expression level of MMP-13 mRNA in chondrocytes of the model group was higher than that of the blank control group(P=0.000),and the relative expression level of COL2A1 mRNA was lower than that of the blank control group(P=0.000).The relative expression level of MMP-13 mRNA in chondrocytes of 40 μmol·L-1 β-ecdysterone group and HIF-1α overexpression negative control group was lower than that of model group(P=0.000,P=0.000),and the relative expression level of COL2A1 mRNA was higher than that of model group(P=0.000,P=0.000).There were no significant difference in the relative mRNA expression levels of MMP-13 and COL2A1 in chondrocytes between the 40 μmol·L-1 β-ecdysterone group and the HIF-1α overexpression negative control group(P=0.993,P=0.999).There was no significant difference in the relative expression level of MMP-13 mRNA in chondrocytes between the HIF-1α overexpression group and the model group(P=0.121),and the relative expression level of COL2A1 mRNA was higher than that in the model group(P=0.043).The relative expression level of VEGF protein in chondrocytes in the model group was lower than that in the blank control group(P=0.000).The relative expression levels of VEGF protein in chondrocytes in the 40 μmol·L-1 β-ecdysterone group and the HIF-1α overexpression negative control group were lower than that in the model group(P=0.000,P=0.000).There was no significant difference in the relative expression level of VEGF protein in chondrocytes between the 40 μmol·L-1 β-ecdysterone group and the HIF-1α overexpression negative control group(P=0.996).The relative expression level of VEGF protein in chondrocytes of HIF-1α overexpression group was higher than that in model group(P=0.000).Conclusion:β-ecdysterone can enhance the viability of IL-1β-induced OA chondrocytes and inhibit their apoptosis,and its mechanism is closely related to the inhibition of the activation of HIF-1α-VEGF signaling pathway.

参考文献/References:

[1] 中华医学会骨科学分会关节外科学组,中国医师协会骨科医师分会骨关节炎学组,国家老年疾病临床医学研究中心(湘雅医院),等.中国骨关节炎诊疗指南(2021年版)[J].中华骨科杂志,2021,41(18):1291-1314.
[2] COACCIOLI S,SARZI-PUTTINI P,ZIS P,et al.Osteoarthritis:new insight on its pathophysiology[J].J Clin Med,2022,11(20):6013.
[3] XU J,QIAN X,DING R.MiR-24-3p attenuates IL-1β-induced chondrocyte injury associated with osteoarthritis by targeting BCL2L12[J].J Orthop Surg Res,2021,16(1):371.
[4] 汪可欣,白敏,宋冰,等.β-蜕皮甾酮调控BMSCs自噬促进成骨分化的作用[J].中国临床药理学杂志,2025,41(4):527-532.
[5] ZHANG X,XU X,XU T,et al.β-Ecdysterone suppresses interleukin-1β-induced apoptosis and inflammation in rat chondrocytes via inhibition of NF-κB signaling pathway[J].Drug Dev Res,2014,75(3):195-201.
[6] ZENG C Y,WANG X F,HUA F Z.HIF-1α in osteoarthritis:from pathogenesis to therapeutic implications[J].Front Pharmacol,2022,13:927126.
[7] LI Z,XIE L,ZOU L,et al.Overexpression of RAD54L attenuates osteoarthritis by suppressing the HIF-1α/VEGF signaling pathway:bioinformatics analysis and experimental validation[J].PLoS One,2024,19(4):e0298575.
[8] LIANG C,XING H,WANG C,et al.Resveratrol protection against IL-1β-induced chondrocyte damage via the SIRT1/FOXO1 signaling pathway[J].J Orthop Surg Res,2022,17(1):406.
[9] DAMGAARD M V,TREEBAK J T.Protocol for qPCR analysis that corrects for cDNA amplification efficiency[J].STAR Protoc,2022,3(3):101515.
[10] YAN P M,LI X,HE Y H,et al.The synergistic protective effects of paeoniflorin and β-ecdysterone against cardiac hypertrophy through suppressing oxidative stress and ferroptosis[J].Cell Signal,2025,125:111509.
[11] PANCHOLI B.Characterization and bioactivity of β-ecdysterone from cell cultures of Trianthema decandra L[J].Indian J Nat Prod Resour,2023,14(4):617-623.
[12] 何哲希,杨嘉飞,姜旭,等.β-蜕皮甾酮调控骨髓间充质干细胞成骨分化对幼兔激素性股骨头坏死的影响[J].中华实用儿科临床杂志,2025,40(3):207-213.
[13] WEN F,YU J,HE C J,et al.β-Ecdysterone protects against apoptosis by promoting autophagy in nucleus pulposus cells and ameliorates disc degeneration[J].Mol Med Rep,2019,19(3):2440-2448.
[14] TANG Y,MO Y,XIN D,et al.β-Ecdysterone alleviates osteoarthritis by activating autophagy in chondrocytes through regulating PI3K/AKT/mTOR signal pathway[J].Am J Transl Res,2020,12(11):7174-7186.
[15] TANG Y H,YUE Z S,XIN D W,et al.β-Ecdysterone promotes autophagy and inhibits apoptosis in osteoporotic rats[J].Mol Med Rep,2018,17(1):1591-1598.
[16] YAN C P,WANG X K,JIANG K,et al.β-Ecdysterone enhanced bone regeneration through the BMP-2/SMAD/RUNX2/Osterix signaling pathway[J].Front Cell Dev Biol,2022,10:883228.
[17] YANG H,HUANG J,MAO Y,et al.Vitexin alleviates interleukin-1β-induced inflammatory responses in chondrocytes from osteoarthritis patients:involvement of HIF-1α path-way[J].Scand J Immunol,2019,90(2):e12773.
[18] SONG S,ZHANG G,CHEN X,et al.HIF-1α increases the osteogenic capacity of ADSCs by coupling angiogenesis and osteogenesis via the HIF-1α/VEGF/AKT/mTOR signaling pathway[J].J Nanobiotechnology,2023,21(1):257.
[19] CHEN B Y,PATHAK J L,LIN H Y,et al.Inflammation triggers chondrocyte ferroptosis in TMJOA via HIF-1α/TFRC[J].J Dent Res,2024,103(7):712-722.
[20] LI W,LIU Y,WEI M,et al.Chondrocyte-targeted α-Solanine through HIF-1α regulating glycolysis to reduce the ferroptosis of chondrocyte in osteoarthritis[J].Int Immuno-pharmacol,2025,159:114841.

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备注/Memo

备注/Memo:
基金项目:国家中医优势专科建设单位项目(国中医药医政函〔2024〕90号); 杭州市生物医药和健康产业发展扶持科技专项(2023WJC234)
通信作者:汤样华 E-mail:tangyanghua168@163.com
(收稿日期:2025-08-12 本文编辑:吕宁)
更新日期/Last Update: 2026-01-20