Journal: bioRxiv
Article Title: A senescent iCAF-like fibroblast state governs therapy resistance in rheumatoid arthritis
doi: 10.64898/2026.04.17.718831
Figure Lengend Snippet: Elimination of senescent cells contributes to the alleviation of experimental synovitis. a , Differential gene expression analysis comparing synovial fibroblasts (SF) depleted of APOC1 or negative control. Blue points, genes with significantly decreased expression (false discovery rate (FDR) < 0.01); black labels, marker genes of p16 h -sn fibroblast from Meguro et al . b , Enrichment of p16 h -sn fibroblast marker genes in APOC1 -depleted SF relative to negative control, calculated by Gene Set Enrichment Analysis (GSEA) . c , Experimental design of the collagen antibody-induced arthritis (CAIA) mouse model using 7-8 week-old male p16-Cre ERT2 -DTR mice or p16-Cre ERT2 mice (control). Starting at the time of arthritis induction, mice received intraperitoneal injections of tamoxifen 80 mg/kg and diphtheria toxin 25 μ g/kg twice daily. d , Clinical arthritis scores of p16-Cre ERT2 -DTR mice (n = 12) and p16-Cre ERT2 control mice (n = 13) under CAIA condition. Dots, mean; error bars, SD. P values, two-tailed Mann-Whitney U test (* p <0.05). e , Ratio of eroded surface to total surface area of left ankle joints in p16-Cre ERT2 -DTR mice (n = 12) and p16-Cre ERT2 control mice (n = 13) under CAIA condition, assessed by micro-computed tomography (micro-CT). Bars, mean; error bars, SD. P values, two-tailed Mann-Whitney U test (* p <0.05). f , Experimental design of the CAIA mouse model using 7-week-old male DBA/1J wild-type mice treated with the TNF inhibitor etanercept and/or the senolytic agent ABT-263. Following arthritis onset, mice received intraperitoneal injections of vehicle or etanercept 2 mg/kg twice daily and oral administration of vehicle or ABT-263 100 mg/kg once daily. g , Clinical arthritis scores of mice treated with etanercept plus ABT-263 (n = 9), etanercept alone (n = 9), ABT-263 alone (n = 8) or vehicle (n = 9) under CAIA condition. Dots, mean; error bars, SD. P values, two-tailed Mann-Whitney U test (* p < 0.01 versus vehicle; # p < 0.05 for etanercept plus ABT-263 versus etanercept alone). h , Ratio of eroded surface to total surface area of left ankle joints in mice treated with etanercept plus ABT-263 (n = 9) or etanercept alone (n = 9) under CAIA condition, assessed by micro-CT. Bars, mean; error bars, SD. P values, two-tailed Mann-Whitney U test (* p <0.05). CAIA, collagen antibody-induced arthritis; CT, computed tomography; DT, diphtheria toxin; DTR, diphtheria toxin receptor; FDR, false discovery rate; GSEA, Gene Set Enrichment Analysis; ip, intraperitoneal; iv, intravenous; KO, knock out; LPS, lipopolysaccharide; po, per os; SD, standard deviation; SF, synovial fibroblast; sn, senescent.
Article Snippet: ABT-263 was dissolved in a vehicle consisting of ethanol (Fujifilm, 054-07225), polyethylene glycol 400 (BioUltra, 91893-250ML-F), and Phosal 50 PG (MedChem Express, HY-H1903) at a ratio of 10:30:60.
Techniques: Gene Expression, Negative Control, Expressing, Marker, Control, Two Tailed Test, MANN-WHITNEY, Micro-CT, Computed Tomography, Knock-Out, Standard Deviation