基于分子对接技术验证6-姜酚通过USP49抑制软骨退行性改变  

Validation of 6-Gingerol in inhibiting cartilage degeneration through USP49 via molecular docking technology

作　　者：杨澜波 苏春霞 赵晓非 杨艳梅 成彦 黄涛 王海彬[3] YANG Lan-bo;SU Chun-xia;ZHAO Xiao-fei;YANG Yan-mei;CHENG Yan;HUANG Tao;WANG Hai-bin(Luoyang Orthopedic-Traumatological Hospital of Henan Province(Henan Provincial Orthopedic Hospital),Luoyang 471002,Henan,China;不详)

机构地区：[1]河南省洛阳正骨医院(河南省骨科医院)运动医学中心,河南洛阳471002 [2]联勤保障部队第989医院骨科,河南洛阳471031 [3]广州中医药大学第一附属医院骨科,广东广州510405

出　　处：《广东医学》2024年第8期970-975,共6页Guangdong Medical Journal

基　　金：河南省中医药科学研究专项基金资助项目(20-21ZY2230)。

摘　　要：目的了解6-姜酚对骨关节炎软骨细胞凋亡及软骨降解的影响及其具体机制。方法筛选出可显著上调USP49表达的中药活性成分(6-姜酚)并进行分子对接。随后,使用不同浓度的6-姜酚处理白细胞介素-1β(IL-1β)诱导的软骨细胞,检测软骨细胞凋亡与泛素特异性蛋白酶49(ubiquitin specific proteases 49,USP49)、β-catenin及软骨降解相关蛋白[基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)、基质金属蛋白酶-13(matrix metalloproteinase-13,MMP-13)]的表达。结果经过筛选,发现6-姜酚可显著促进USP49表达,分子对接显示6-姜酚与USP49可高效结合。不同浓度的6-姜酚处理IL-1β诱导的软骨细胞后,可显著上调USP49表达,抑制细胞凋亡及β-catenin、MMP-1与MMP-13表达。结论6-姜酚通过上调USP49表达调控Wnt/β-catenin信号转导通路,抑制软骨细胞凋亡及软骨降解相关蛋白MMP-1,MMP-13的表达,进而缓解IL-1β诱导的软骨退行性改变。Objective To understand the effects and underlying mechanisms of 6-gingerol on chondrocyte apoptosis and cartilage degradation in osteoarthritis.Methods The active components of traditional Chinese medicine that significantly upregulate USP49 expression(6-gingerol)were screened and subjected to molecular docking.Subsequently,IL-1β-induced chondrocytes were treated with different concentrations of 6-gingerol,and the apoptosis of chondrocytes and the expression of USP49,β-catenin,and cartilage degradation-related proteins(MMP-1,MMP-13)were detected.Results The screening revealed that 6-gingerol significantly promotes the expression of USP49.Molecular docking showed a high-efficiency binding between 6-gingerol and USP49.After treating IL-1β-induced chondrocytes with different concentrations of 6-gingerol,the expression of USP49 was significantly upregulated,and the apoptosis of chondrocytes and the expression ofβ-catenin,MMP-1,and MMP-13 were inhibited.Conclusion 6-gingerol regulates the Wnt/β-catenin signaling pathway by upregulating USP49 expression,inhibits chondrocyte apoptosis and the expression of cartilage degradation-related proteins MMP-1 and MMP-13,thereby alleviating IL-1β-induced cartilage degeneration.

关 键 词：6-姜酚 泛素特异性蛋白酶-49 分子对接 WNT/Β-CATENIN通路 

分 类 号：R684.3[医药卫生—骨科学] R274.9[医药卫生—外科学]