Expression and mechanism of GJA1 gene in osteoarthritic chondrocytes
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.
NETL
NSTL
万方数据
