ApoEVs ameliorate osteoporosis via Ras signal. (A) Schematic view of the experimental procedure. Control siRNA ApoEVs and RasKD ApoEVs were injected into OVX mice weekly for two months. (B-C) Three-dimensional reconstruction images of μCT illustrating bone microarchitecture in the distal femur, and quantitative analysis of BV, BV/TV, and BMD. n=5 biologically independent animals per group. (D) HE and (E) Masson depicting fewer osteoblast-like cells at the growth plate metaphysis in RasKD ApoEVs treated mice. Scale bar: 100 μm and 50 μm (D); 50μm (E). (F) Calcein double labeling indicating a slower bone formation rate per bone surface in RasKD ApoEVs group. (G) IHC staining visualizing lower expression of OPN in RasKD ApoEVs group. Scale bar: 20 μm. (H) Schematic view of the experimental procedure. Control lentivirus ApoEVs and RasOE ApoEVs were injected into OVX mice weekly for two months. (I-J) Three-dimensional reconstruction images of μCT depicting bone microarchitecture in the distal femur, and quantitative analysis of BV, BV/TV, and Tb.N. n=4 biologically independent animals per group. (K) HE and (L) Masson staining revealing more osteoblast-like cells at the growth plate metaphysis in RasOE ApoEVs treated mice. Scale bar: 100 μm and 50 μm (K); 50μm (L). (M) Calcein double labeling demonstrating a faster bone formation rate per bone surface in the RasOE ApoEVs group. (N) IHC staining showing lower expression of OPN in RasOE ApoEVs group. Scale bar: 20 μm. Data are means ± SEMs. Statistical significance was determined by two-tailed paired t-test in (C, F, J, M). Not significant (ns) = P > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.