Fig. 2: PKA activation induces FD-like lesions, while its inhibition halts GαsR201C-induced FD lesions.
From: Protein kinase A is a dependent factor and therapeutic target in mouse models of fibrous dysplasia
a A summary table listing the genotypes, targeted molecules, and Dox dosage regimens for each transgenic mouse line used in this study. PKI4A is a nonsense mutant of PKI. b Representative hindlimb images of Tet-PKAcαW197R/Prrx1-Cre (PKA mice), Tet-GαsR201C/Tet-PKI4A/Prrx1-Cre (FD-PKI4A mice), Tet-GαsR201C/Tet-PKI/Prrx1-Cre (FD-PKI mice), and littermate controls. c Kaplan‒Meier curve of mice free from visible FD-like symptoms (limb swelling and reduced mobility, biologically independent samples, two-tailed log-rank test). d μCT images of hindlimb bones showing ground-glass deformities (red arrows) in PKA and FD-PKI4A mice, which were not observed in FD-PKI mice. e Representative images of three-dimensional (3D) reconstructions of tibias showing expansile lesions in PKA and FD-PKI4A mice. f Representative 3D reconstructions of skulls revealing bone defects in PKA and FD-PKI4A mice. g Quantitative μCT analyses of the bone volume fraction (BV/TV) and bone mineral density (BMD) in defined ROIs of PKA, FD-PKI4A, FD-PKI, and littermate controls (Control n = 17, PKA n = 5, FD-PKI4A n = 6 and FD-PKI n = 6, biologically independent samples, one-way ANOVA with Tukey’s multiple comparisons test). h Histopathological examination (H&E, von Kossa, and Sirius red staining) of tibias showing FD-like lesions in PKA and FD-PKI4A mice. Lesions include multinucleated osteoclasts (black arrows) located on the surface of irregular woven bone (black stars), osteoid deposition lining the woven bone surfaces (white arrows), and disorganized woven bone lacking osteoblast rimming and embedded within a collagen-rich fibrocellular matrix (white stars). In contrast, FD-PKI and control mice exhibit dense cortical bone with defined boundaries (dashed lines). Sirius red staining reveals disorganized woven bone and type III collagen fibrosis in PKA and FD-PKI4A mice. Three independent experiments were performed. 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.
