Fig. 6: Anti-arthritic actions of BMS are associated with SF senescence. | Nature Communications

Fig. 6: Anti-arthritic actions of BMS are associated with SF senescence.

From: Therapeutic senescence via GPCR activation in synovial fibroblasts facilitates resolution of arthritis

Fig. 6

a Arthritis was induced in C57BL/6NCrl mice with two injections of 100 μl KBN serum on day 0 and day 2. BMS was administered intraperitoneally daily at the dose of 18 mg/kg from day 3. Clinical score and paw swelling were recorded daily. Data are mean ± SE (n = 5, Student’s t-test vs. control day 9, Ctrl; *p < 0.05, **p < 0.01). b p16INK4 expression was assessed by immunofluorescence on EDTA-decalcified and paraffin-embedded knee joint sections. p16INK4 immunostaining is shown in pink while nuclear staining with DAPI is in blue. Scale bars indicate 100 μm. c Arthritis was induced with two injections of 150 μl KBN serum on days 0 and 2. BMS was administered intraperitoneally at a daily dose of 18 mg/kg from day 3. From day 4, senolytics (Sen, dasatinib + quercetin at doses of 2.5 and 10 mg/kg, respectively) were administered intraperitoneally on alternate days. Data are mean ± SE (n = 5, Student’s t-test vs. control at day 9, Ctrl; *p < 0.05). d p16INK4 expression was assessed by immunofluorescence on EDTA-decalcified and paraffin-embedded knee joints sections. p16INK4 is shown in pink. Arrows and dotted lines indicate synovial lining. e Co-localization by immunofluorescence of senescence marker p16INK4 and the SF marker cadherin-11, Cad11, in knee joins of arthritic mice treated with BMS. Scale bars indicate 100 μm. f Representative images of H&E (ankle joints) and Toluidine blue (knee joints) staining, indicating the degree of cell infiltration (H&E) and cartilage integrity (Toluidine blue) in control and BMS-treated mice. Data are mean ± SE (n = 5). g The extent of cell infiltration and cartilage damage were combined in a cumulative damage score (max = 6). Data values are mean ± SE (n = 5). Scale bars indicate 2.5 mm and 500 μm for H&E, and 1 mm and 100 μm for Toluidine blue. Source data are provided as Source Data file.

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