GJA1在骨关节炎软骨细胞中表达及作用机制研究
Expression and mechanism of GJA1 gene in osteoarthritic chondrocytes
孙俊魁 1邱赞 2王新威 2李劲峰 1史健翔 2刘宏建1
作者信息
- 1. 郑州大学第一附属医院骨科医学部,郑州 450052
- 2. 郑州大学河南省医学科学研究院,郑州 450052
- 折叠
摘要
目的 通过筛选骨关节炎(OA)中差异表达离子通道相关基因(IRGs),为其治疗提供新策略.方法 使用骨关节炎软骨细胞单细胞转录组测序数据(HRA002569)和软骨组织转录组测序数据(GSE168505),分析323个IRGs表达情况,筛选到1个骨关节炎上调的离子通道相关基因GJA1(编码connexin43蛋白,CX43).对应激型软骨细胞进行拟时序分析,解析GJA1在不同状态应激型软骨细胞的生物学功能.通过文献检索,筛选CX43抑制剂;利用alphafold3和RFdiffusion方法,设计CX43结合短肽.使用Wilcoxon秩和检验进行差异表达检验,使用Bonferroni法进行P值校正.结果 通过OA单细胞和常规转录组数据分析,与323个IRGs取交集,GJA1在OA患者受损软骨细胞中显著上调(log2FC=0.278,校准P＜0.01).GJA1在OA发展中起重要作用.文献检索结果显示氯苯吩嗪可能是CX43特异性抑制剂;利用机器学习方法,设计4条结合短肽靶向抑制CX43,为OA治疗提供新策略.结论 GJA1在OA患者应激型软骨细胞中表达上调,与OA发展和疼痛相关.
Abstract
Objective By analyzing single-cell and bulk cell transcriptome sequencing data of os-teoarthritis(OA),to screen ion channel-related genes differentially expressed in OA,providing new strate-gies for its treatment.Methods Sing single-cell transcriptome sequencing data of osteoarthritic chondro-cytes(HRA002569)and transcriptome sequencing data of cartilage tissue(GSE168505)were used.The expression of 323 ion channel-related genes(IRGs)was analyzed.The gap junction protein alpha 1[GJA1,encoding connexin 43 protein(CX43)]as an OA-related IRG was identified.Pseudotime analysis was performed on stress-induced chondrocytes to elucidate the biological function of GJA1 in different states of stress-induced chondrocytes.Through literature search,CX43 inhibitors were screened.Using al-phafold2,alphafold3,and RFdiffusion methods,Cx43-binding peptides were designed to provide new strat-egies for targeting CX43 inhibition.Results Through the analysis of OA single-cell and conventional tran-scriptome sequencing,323 IRGs were screened,and GJA1 was found to be significantly upregulated in damaged chondrocytes of OA patients(log2FC=0.278,P＜0.01).GJA1 plays an important role in the development of OA.Using machine learning methods,four high-affinity peptides targeting CX43 inhibition were designed,providing new strategies for OA treatment.Conclusion GJA1 is upregulated in stress-in-duced chondrocytes of OA patients and is associated with the development and pain of OA.
关键词
骨关节炎/软骨细胞/离子通道Key words
Osteoarthritis/Chondrocytes/Ion channels引用本文复制引用
基金项目
郑州大学河南省医药科学研究院科研培育项目(2024BP0207)
出版年
2024
NETL
NSTL
万方数据