Fig. 6
From: FGFR antagonists restore defective mandibular bone repair in a mouse model of osteochondrodysplasia
Defective bone repair with pseudarthrosis in Fgfr3N534K/+ mice is rescued by BMN111 and BGJ398. a Schematic representations of BMN111 and BGJ398 injections in Fgfr3N534K/+ mice, from day 0 to day 14 post-fracture. Representative 3D coronal views of µCT scans at day 14 post-fracture of Fgfr3+/+ and Fgfr3N534K/+ mice. Graphical representation of BV/TV in the calluses of Fgfr3+/+ and Fgfr3N534K/+ mice. Graphical representation of the callus volumes of Fgfr3+/+ and Fgfr3N534K/+ mice: Fgfr3+/+ + vehicle (n = 10), Fgfr3N534K/+ + vehicle (n = 9), Fgfr3N534K/+ + BMN111 (n = 8) and Fgfr3N534K/+ + BGJ398 (n = 7). b Representative images of the callus at day 14 post-fracture in Fgfr3+/+ and Fgfr3N534K/+ mice (Sirus Red/Alcian Blue staining). Representative images of collagen II, collagen X, TUNEL/DAPI and collagen I immunolabelling of the callus from Fgfr3+/+ and Fgfr3N534K/+mice. Scale bar: 200 µm. Graphical representation of collagen-X-positive chondrocyte/collagen-II-positive chondrocyte ratio: Fgfr3+/+ + vehicle (n = 8), Fgfr3N534K/+ + vehicle (n = 8) Fgfr3N534K/+ + BMN111 (n = 7), and Fgfr3N534K/+ + BGJ398 (n = 7). Graphical representation of TUNEL- and DAPI-positive cells in the hypertrophic chondrocyte area of the callus (in %): Fgfr3+/+ + vehicle (n = 7), Fgfr3N534K/+ + vehicle (n = 8), Fgfr3N534K/+ + BMN111 (n = 8), and Fgfr3N534K/+ + BGJ398 (n = 7). Graphical representation of intertrabecular area/total bone callus area ratio (collagen I staining): Fgfr3+/++ vehicle (n = 6) Fgfr3N534K/+ + vehicle (n = 8), Fgfr3N534K/+ + BMN111 (n = 7) and Fgfr3N534K/+ + BGJ398 (n = 7). NS: non-significant, *P < 0.05, **P < 0.01, ***P < 0.005. c Schematic representation of BMN111 and BGJ398 injections in Fgfr3N534K/+ mutant mice from day 0 to day 28 post-fracture. Representative 3D coronal views of µCT scans at day 28 post-fracture showing the mandibular fracture site (white arrow). Representative images (Sirus Red/Alcian Blue staining) of the calluses at day 28 post-fracture from Fgfr3+/+ + vehicle, Fgfr3N534K/+ + vehicle, Fgfr3N534K/+ + BMN111, and Fgfr3N534K/+ + BGJ398, showing pseudarthrosis (PA) within the callus and persistent cartilage (blue) in Fgfr3N534K/+ mice, and continuous bone callus (total bridging) in Fgfr3+/+ + vehicle, Fgfr3N534K/+ + BMN111 and Fgfr3N534K/+ + BGJ398 mice. Scale bar: 1 mm. d Graphical representation of BV/TV of the calluses and the callus volume from Fgfr3+/+ and Fgfr3N534K/+ mice showing the benefit effect of the treatment. A graphical representation of consolidation grades after 28 days of treatment (grade 1: total bone union; grade 2: bone union with minor bone defects; grade 3: partial bone union with major bone defects; grade 4: non-union). Fgfr3+/+ + vehicle (n = 12), Fgfr3N534K/+ + vehicle (n = 14), Fgfr3N534K/+ + BMN111 (n = 9), and Fgfr3N534K/+ + BGJ398 (n = 10). e Representative images of TRAP-labeling at day 28 post-fracture in Fgfr3+/+ and Fgfr3N534K/+ callus. Scale bar: 100 µm. Graphical representation of the osteoclast count (osteoclasts per mm) at the edge of the calluses: Fgfr3+/++ vehicle (n = 6), Fgfr3N534K/+ + vehicle (n = 6), Fgfr3N534K/+ + BMN111 (n = 7), and Fgfr3N534K/+ + BGJ398 (n = 6). NS: non-significant, *P < 0.05, **P < 0.01, ***P < 0.005, ****P < 0.000 5
