To use the single-cell RNA sequencing results (GSE152815) of obese and normal-weight hip arthritis synovial tissues in gene expression omnibus(GEO) database to analyze the differences in cell composition and function between the two, and to explore their metabolic reprogramming and the imbalance of microenvironment homeostasis, in order to provide references for researchers in related fields.

Using the GSE152815 data in the GEO database, through quality control, unsupervised clustering, trajectory analysis, gene enrichment analysis, gene regulatory network analysis and other methods, Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used to determine the statistical significance of differences in gene expression.

Through quality control, unsupervised clustering, and according to the marker molecules of each subgroup, synovial tissue can be divided into four groups, namely synovial fibroblast progenitor cells (SFPCs), synovial hypertrophic chondrocytes (SHTCs), synovial fibroblast cells (SFBs) and synovial fibrochondrocytes (SFCs). Trajectory analysis found that SFPCs can differentiate into SFBs and SFCs. During the differentiation process, the expression of fatty acid metabolism-related genes-apolipoprotein E (APOE) and ATP binding cassette transporter A1 (ABCA1) gradually increase(Z =25.17, 17.89, both P<0.05), while the ability to metabolize glucose gradually declines(Z =15.32, P<0.05). Analysis of single-cell gene regulatory network found that transcription factors [SRY-box transcription factor 4(SOX4) and microphthalmia-associated transcription factor (MITF)] could regulate cell fatty acid metabolism by co-regulating molecules such as APOE and ABCA1.

The results confirmed that the microenvironment disorder of the synovial membrane of obese patients and normal-weight patients will cause the metabolic disorder of some synovial cells, reprogramming from the original glucose metabolism to fatty acid metabolism, which may be closely related to genes such as APOE and ABCA1 regulated by transcription factor SOX4 and MITF. Clarifying the changes of metabolic reprogramming in these cells will help to study the influence of different metabolic reprogramming on cell function, and provide ideas and new ways for studying metabolic reprogramming of osteoarthritis and other diseases.