Aged bone matrix-derived extracellular vesicles as a messenger for calcification paradox

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 () and Hui Xie ()
Additional contact information
Zhen-Xing Wang: Central South University
Zhong-Wei Luo: Central South University
Fu-Xing-Zi Li: Central South University
Jia Cao: Central South University
Shan-Shan Rao: Central South University
Yi-Wei Liu: Central South University
Yi-Yi Wang: Central South University
Guo-Qiang Zhu: Central South University
Jiang-Shan Gong: Central South University
Jing-Tao Zou: Central South University
Qiang Wang: Zhejiang University School of Medicine, Hangzhou
Yi-Juan Tan: Central South University
Yan Zhang: Central South University
Yin Hu: Central South University
You-You Li: Central South University
Hao Yin: Central South University
Xiao-Kai Wang: Central South University
Ze-Hui He: Central South University
Lu Ren: Central South University
Zheng-Zhao Liu: Central South University
Xiong-Ke Hu: Central South University
Ling-Qing Yuan: Central South University
Ran Xu: Central South University
Chun-Yuan Chen: Central South University
Hui Xie: Central South University

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-29191-x

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