Fig. 6

E-sEVs prevent VPA-induced bone loss. Mice aged eight weeks were treated with vehicle or VPA in combination with sEVs (VPA+sEVs) or E-sEVs (VPA + E-sEVs) for four weeks. a H&E staining of distal femur sections (n = 5). Scar bar: 1 mm and 100 μm. b Quantitative assessment of Tb.N in (a). c Micro-CT images of the femurs from control, VPA, VPA+sEVs and VPA + E-sEVs groups (n = 5). d Morphometric analyses of trabecular bone. e, f TRAP staining of the femurs isolated from mice subjected to various treatments and the corresponding quantification (n = 3). Scar bar: 100 μm. g Micro-CT images in the lumbar spine after corresponding treatments (n = 5). h Corresponding morphometric measurements of trabecular bone in (g). i, j TRAP staining of the lumbar spine sections and quantification of TRAP-positive cells (n = 3). Scar bar: 100 μm. k Schematic diagram showing the proposed mechanism of VPA-induced bone loss and how E-sEVs prevent it. Data are presented as the mean ± SEM (n ≥ 3) (*p < 0.05; **p < 0.01; ***p < 0.001)