Abstract
AbstractBackgroundInadequate osteogenesis and excessive adipogenesis of bone marrow mesenchymal stem cells (BMSCs) are key factors in the pathogenesis of osteoporosis. Patients with Alzheimer’s disease (AD) have a higher incidence of osteoporosis than healthy adults, but the underlying mechanism is not clear. The aim of this study was to investigate the role of brain‐derived extracellular vesicles (EVs) from AD mice on the regulation of bone metabolism.MethodBrain‐derived EVs from AD or wide‐type mice was injected into C57BL/6 mice intravenously once a week for two months.ResultHere, we show that brain‐derived EVs from adult AD or wild‐type mice can cross the blood‐brain barrier to reach the distal bone tissue, while only AD brain‐derived EVs (AD‐B‐EVs) significantly promote the shift of the BMSC differentiation fate from osteogenesis to adipogenesis and induce a bone‐fat imbalance. MiR‐483‐5p is highly enriched in AD‐B‐EVs, brain tissues from AD mice, and plasma‐derived EVs from AD patients. This miRNA mediates the anti‐osteogenic, pro‐adipogenic, and pro‐osteoporotic effects of AD‐B‐EVs by inhibiting Igf2.ConclusionThis study identifies the role of B‐EVs as a promoter of osteoporosis in AD by transferring miR‐483‐5p.
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