Fig. 4
Genetic and pharmacological inhibition of TrkA signaling impairs vascular ingrowth after soft tissue trauma. a Schematic representation of experiment. (Created in Biorender.com). TrkAF592A mice have a point mutation which renders them susceptible to temporally controllable inhibition of TrkA catalytic activity, via administration of the small molecule 1NMPP1. Either TrkAWT or TrkAF592A animals (6–8 weeks old, male and female mice) were subjected to HO induction and both administered 1NMPP1 throughout the study period. Analyses performed at 21 d post-injury. b–d Representative immunohistochemical staining for TUBB3 (Beta III Tubulin, appearing green) and quantification among TrkAWT or TrkAF592A animals, as assessed at the distal tenotomy site as visualized using sagittal cross-sections. e–g Representative immunostaining for CD31 (appearing red) and quantification among TrkAWT or TrkAF592A animals. h–j EMCN (Endomucin) and CD146 co-immunohistochemical staining (appearing red and white) and quantification among TrkAWT or TrkAF592A animals. k Schematic representation of experiment. C57BL/6 J mice (6–8 weeks old, male and female mice) were administered AR786 or vehicle control throughout the study period. HO induction was performed (burn/tenotomy), with analysis at day 21. l–n Representative immunohistochemical staining for TUBB3 and quantification among control or AR786 treated animals, as assessed at the distal tenotomy site. o–q Representative immunostaining for CD31 (appearing red) and quantification among control or AR786 treated animals. Dashed white lines indicate edges of Achilles tendon. Scale bars: 100 μm. n = 4–5 animals per group. Individual dots in scatterplots represent values from single animal measurements, while mean and one SD are indicated by crosshairs and whiskers. * P < 0.05; ** P < 0.01. A two-tailed student’s t test was used for all comparisons
