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.© 2022. The Author(s).
About The Expert
Zhen-Xing Wang
Zhong-Wei Luo
Fu-Xing-Zi Li
Jia Cao
Shan-Shan Rao
Yi-Wei Liu
Yi-Yi Wang
Guo-Qiang Zhu
Jiang-Shan Gong
Jing-Tao Zou
Qiang Wang
Yi-Juan Tan
Yan Zhang
Yin Hu
You-You Li
Hao Yin
Xiao-Kai Wang
Ze-Hui He
Lu Ren
Zheng-Zhao Liu
Xiong-Ke Hu
Ling-Qing Yuan
Ran Xu
Chun-Yuan Chen
Hui Xie
References
PubMed