Fig. 3: Prevention of bone and growth cartilage alterations after AAV9-Galns administration.
Four-weeks-old MPSIVA rats were treated with 6.67 × 1013 vg/kg AAV9-Galns vectors. a Expression of optimized rat Galns (orGalns) in bones of 2-months-old WT (n = 2) and AAV9-Galns-treated MPSIVA (n = 4) rats. b Femoral GALNS activity in 6-months-old WT, untreated and AAV9-Galns-treated MPSIVA rats. WT activity was set to 100%, corresponding to 135.56 ± 44.81 nmol/17 h/mg (n = 3 animals/group). c, d KS content in the femoral and tibial growth plate (GP) and diaphysis in the same cohort as in b. e Histological analysis of humerus GP sections stained with Safranin O from 2-months-old WT (n = 5), untreated (n = 11), and AAV9-Galns-treated (n = 4) MPSIVA rats. Scale bars: 100 µm. f Toluidine-blue staining of semithin sections of tibial GP from 6-months-old WT, untreated and AAV9-Galns-treated MPSIVA rats. Treated rats showed a reduction of hypertrophic chondrocytes in resting (arrows) and proliferative (arrowheads) zones (n = 3 animals/group). Scale bars, 50 µm. g Ultrastructural analysis by TEM of tibial proliferative chondrocytes of the same cohort as in f. AAV9-Galns treatment cleared most intracellular storage vesicles (arrows). Scale bars: 10 µm. h–j Analysis by μCT of bone mineral content (BMC), bone mineral density (BMD), tissue mass content (TMC), tissue mass density (TMD), bone volume/tissue volume (BV/TV), bone surface/bone volume (BS/BV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular spacing (Tb.Sp) of femoral trabecular (h, i) bone of 2-months-old WT (n = 5), untreated (n = 4) and AAV9-Galns-treated (n = 5) MPSIVA rats, and compact (j) bone of 2-months-old WT (n = 3), untreated (n = 4) and AAV9-Galns-treated (n = 5) MPSIVA rats. All results are shown as mean ± SEM and P-values of one-way Anova test are indicated (95% confidence interval). *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 vs. untreated MPSIVA rats. ND non-detected. Source data are provided as a Source Data file.
