期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-29191-x
关键词
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资金
- National Natural Science Foundation of China [81801395, 82072504, 81871822, 81522012, 81670807, 81702237, 81600699, 81701383, 81974127]
- Innovation Driven Project of Central South University [2019CX014, 2018CX029]
- Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019-RC-HL-024]
- Science and Technology Plan Project of Hunan Province [2017XK2039, 2018RS3029]
- Science and Technology Innovation Program of Hunan Province [2020RC4008]
- Hunan Province Natural Science Foundation of China [2020JJ4914, 2017JJ3501, 2020JJ5883, 2020JJ5900]
- China Postdoctoral Science Foundation [2019T120717, 2017M612596, 2018M632998, 2020T130142ZX]
- Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University) Ministry of Education Open Funding [201813]
- Hunan Provincial Innovation Foundation for Postgraduate [CX2018B045, CX20190148]
- Free Exploration Program of Central South University [502221901]
This study uncovers the role of extracellular vesicles from bone matrix as a messenger in the development of osteoporosis and vascular calcification (calcification paradox) during skeletal aging and menopause by transferring miR-483-5p and miR-2861.
Adipocyte differentiation of bone marrow mesenchymal stem/stromal cells (BMSCs) instead of osteoblast formation contributes to age- and menopause-related marrow adiposity and osteoporosis. Vascular calcification often occurs with osteoporosis, a contradictory association called calcification paradox. Here we show that extracellular vesicles derived from aged bone matrix (AB-EVs) during bone resorption favor BMSC adipogenesis rather than osteogenesis and augment calcification of vascular smooth muscle cells. Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. Alendronate (ALE), a bone resorption inhibitor, down-regulates AB-EVs release and attenuates aging- and ovariectomy-induced bone-fat imbalance. In the VD3-treated aged mice, ALE suppresses the ovariectomy-induced aggravation of vascular calcification. MiR-483-5p and miR-2861 are enriched in AB-EVs and essential for the AB-EVs-induced bone-fat imbalance and exacerbation of vascular calcification. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring miR-483-5p and miR-2861. This study uncovers the role of extracellular vesicles from bone matrix as a messenger in the development of osteoporosis and vascular calcification (calcification paradox) during skeletal aging and menopause by transferring miR-483-5p and miR-2861.
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