Exosome-guided bone targeted delivery of Antagomir-188 as an anabolic therapy for bone loss.
basic_science · Level V
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- Record sourced from PubMed, PMID 33718671.
- Also identified by DOI 10.1016/j.bioactmat.2021.02.014 and PMC identifier 7917458.
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Abstract
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<sup>+</sup> exosomes selectively accumulated in the bone marrow. Then, we fused CXCR4<sup>+</sup> 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.