摘要
The differentiation shift from osteogenesis to adipogenesis of bone marrow mesenchymal stem cells(BMSCs)characterizes many pathological bone loss conditions.Stromal cell-derived factor-1(SDF1)is highly enriched in the bone marrow for C-X-C motif chemokine receptor 4(CXCR4)-positive hematopoietic stem cell(HSC)homing and tumor bone metastasis.In this study,we displayed CXCR4 on the surface of exosomes derived from genetically engineered NIH-3T3 cells.CXCR4+exosomes selectively accumulated in the bone marrow.Then,we fused CXCR4+exosomes with liposomes carrying antagomir-188 to produce hybrid nanoparticles(NPs).The hybrid NPs specifically gathered in the bone marrow and released antagomir-188,which promoted osteogenesis and inhibited adipogenesis of BMSCs and thereby reversed age-related trabecular bone loss and decreased cortical bone porosity in mice.Taken together,this study presents a novel way to obtain bone-targeted exosomes via surface display of CXCR4 and a promising anabolic therapeutic approach for age-related bone loss.
基金
This work was supported by grants from National Key R&D Program of China(No.2018YFC2001500)
National Natural Science Foundation of China(No.91749204,81771491 to J.Su,and 81871099 to X.Chen).
