MiR-497∼195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch and HIF-1α activity

Mi Yang, Chang-Jun Li, Xi Sun, Qi Guo, Ye Xiao, Tian Su, Man-Li Tu, Hui Peng, Qiong Lu, Qing Liu, Hong-Bo He, Tie-Jian Jiang, Min-Xiang Lei, Mei Wan, Xu Cao () and Xiang-Hang Luo ()
Additional contact information
Mi Yang: Endocrinology Research Center, Xiangya Hospital of Central South University
Chang-Jun Li: Endocrinology Research Center, Xiangya Hospital of Central South University
Xi Sun: Endocrinology Research Center, Xiangya Hospital of Central South University
Qi Guo: Endocrinology Research Center, Xiangya Hospital of Central South University
Ye Xiao: Endocrinology Research Center, Xiangya Hospital of Central South University
Tian Su: Endocrinology Research Center, Xiangya Hospital of Central South University
Man-Li Tu: Endocrinology Research Center, Xiangya Hospital of Central South University
Hui Peng: Endocrinology Research Center, Xiangya Hospital of Central South University
Qiong Lu: Endocrinology Research Center, Xiangya Hospital of Central South University
Qing Liu: Xiangya Hospital, Central South University
Hong-Bo He: Xiangya Hospital, Central South University
Tie-Jian Jiang: Endocrinology Research Center, Xiangya Hospital of Central South University
Min-Xiang Lei: Endocrinology Research Center, Xiangya Hospital of Central South University
Mei Wan: Johns Hopkins University School of Medicine
Xu Cao: Johns Hopkins University School of Medicine
Xiang-Hang Luo: Endocrinology Research Center, Xiangya Hospital of Central South University

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31hiEmcnhi), is identified as coupling angiogenesis and osteogenesis. The abundance of type CD31hiEmcnhi vessels decrease during ageing. Here we show that expression of the miR-497∼195 cluster is high in CD31hiEmcnhi endothelium but gradually decreases during ageing. Mice with depletion of miR-497∼195 in endothelial cells show fewer CD31hiEmcnhi vessels and lower bone mass. Conversely, transgenic overexpression of miR-497∼195 in murine endothelium alleviates age-related reduction of type CD31hiEmcnhi vessels and bone loss. miR-497∼195 cluster maintains the endothelial Notch activity and HIF-1α stability via targeting F-box and WD-40 domain protein (Fbxw7) and Prolyl 4-hydroxylase possessing a transmembrane domain (P4HTM) respectively. Notably, endothelialium-specific activation of miR-195 by intravenous injection of aptamer-agomiR-195 stimulates CD31hiEmcnhi vessel and bone formation in aged mice. Together, our study indicates that miR-497∼195 regulates angiogenesis coupled with osteogenesis and may represent a potential therapeutic target for age-related osteoporosis.

Date: 2017
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DOI: 10.1038/ncomms16003

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