期刊
BIOACTIVE MATERIALS
卷 6, 期 9, 页码 2905-2913出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.02.014
关键词
Exosomes; Bone targeting; miR-188; CXCR4; Osteoporosis
资金
- National Key R&D Program of China [2018YFC2001500]
- National Natural Science Foundation of China [91749204, 81771491, 81871099]
This study demonstrates a novel approach to target bone marrow through surface display of CXCR4 on exosomes, which are then fused with liposomes carrying antagomir-188 to produce hybrid nanoparticles. These nanoparticles selectively accumulate in bone marrow, release antagomir-188, promote osteogenesis, inhibit adipogenesis, and reverse bone loss conditions, presenting a promising therapeutic strategy for age-related bone loss.
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.
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