Research Paper Volume 14, Issue 15 pp 6006—6027

Senolytic drugs relieve pain by reducing peripheral nociceptive signaling without modifying joint tissue damage in spontaneous osteoarthritis

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Figure 3. Senolytics treatment (ABT263 and D+Q) decreases the projection of nociceptive neuro-fiber in the synovium in spontaneous OA in aged mice. (A) Representative immunofluorescence images for CGRP, NGF, and TrkA in the synovium of 21 to 22-month-old mice were administered ABT263 or Veh (synovium indicated by dashed lines). Quantification of (B) density of CGRP+ nerve fibers (n = 3 mice for Veh, n = 5 mice for ABT263), (C) NGF positive area (n = 3 for Veh, n = 5 for ABT263), (D) relative mRNA levels of NGF in the joints (n = 4 for Veh, n = 7 for ABT263), and (E) density of TrkA+ nerve fibers in the mouse joint synovium (positive for each marker indicated by arrows) (n = 3 for Veh, n = 5 for ABT263). (F) Images of immunostaining of CGRP+ neuro-fibers, NGF expressions, and TrkA+ fibers. Quantitative analysis of the (G) density of CGRP+ sensory nerve fibers (n = 5 per group) and (H) NGF positive area in the synovium of aged mice administered D+Q (n = 5 for Veh, n = 7 for D+Q). (I) Relative mRNA levels of NGF in the joints (n = 4 for Veh, n = 6 for D+Q). (J) Quantitative analysis of the density of TrkA+ nerve fibers in the synovium of aged mice after D+Q administration (n = 5 for Veh, n = 7 for D+Q). Relative mRNA levels of VEGF and ATF4 in the joint of (K) ABT263 or Veh (n = 4 for Veh, n = 7 for ABT263) and (L) D+Q or Veh-treated older mice (n = 4 for Veh, n = 6 for D+Q). Whisker plots represent the 10th and 90th percentiles, and the line corresponds to the median. * p < 0.05, ** p < 0.01; Unpaired Student’s t-test. Scale bars, 50 μm.