Fig. 6: Pharmacological inhibition of PKA alleviates FD-like bone lesions and improves bone strength.
From: Protein kinase A is a dependent factor and therapeutic target in mouse models of fibrous dysplasia
a Therapeutic regimen outlining Dox and PKA inhibitor administration in GαsR201C/LSL-rtTA/Prrx1-Cre (FD mice), along with the timing of sample collection (V video, H histology, TC tissue collection, SC serum collection). b qPCR analysis at T2 showing GNAS mRNA expression in limb bones (Control n = 7, FD n = 11, FD + H89 n = 4 and FD + Rp-8-Br-cAMPs n = 4, biologically independent samples, one-way ANOVA with Tukey’s multiple comparisons test). c Immunoblotting at T2 demonstrating PKA phosphorylation in limb bones. Three independent experiments were performed. d Representative limb images at T2 of FD mice, FD + H89 mice, FD + Rp-8-Br-cAMPs mice and littermate controls. e Kaplan‒Meier curve showing the persistence of FD-like symptoms (limb swelling and limping behavior) in the FD group (n = 11), whereas the FD + H89 (n = 11) and FD + Rp-8-Br-cAMPs (n = 7) groups presented a reversal of symptoms within 1 week of PKA inhibitor treatment (biologically independent samples, two-tailed log-rank test). f μCT images of hindlimb at T2 showing more pronounced ground-glass deformities (red arrows) in FD mice compared to FD + H89 mice and FD + Rp-8-Br-cAMPs mice. g Representative three-dimensional (3D) reconstructions of limb bone at T2 showing reduced expansile lesions in FD + H89 mice and FD + Rp-8-Br-cAMPs mice relative to FD mice. h Representative 3D reconstructions of skulls at T2. i Quantitative μCT analyses of the bone volume fraction (BV/TV) and bone mineral density (BMD) in FD mice, FD + H89 mice, FD + Rp-8-Br-cAMPs mice, and littermate controls (Control n = 9, FD n = 6, FD + H89 n = 4 and FD + Rp-8-Br-cAMPs n = 5, biologically independent samples, two-way ANOVA with Sidak’s multiple comparisons test). j Representative of load-displacement curves of tibias at T2 obtained from compression testing, with arrowhead marking the fracture point. k Biomechanical analyses of tibias at T2 showing maximum load and elastic modulus in FD mice, FD + H89 mice, FD + Rp-8-Br-cAMPs mice and controls (Control n = 4, FD n = 6, FD + H89 n = 5 and FD + Rp-8-Br-cAMPs n = 4, biologically independent samples, one-way ANOVA with Tukey’s multiple comparisons test). The data are presented as box-and-whisker plots, with boxes representing the interquartile range (25th–75th percentiles), the minimum and maximum values reached by bars, the median plotted as a line in the middle, and the mean marked as “+”. Source data are provided as a Source Data file.
