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Nat Commun. 2017 Jul 7;8:16003. doi: 10.1038/ncomms16003.

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

Yang M1,2, Li CJ1,2, Sun X1,3, Guo Q1,4, Xiao Y1, Su T1, Tu ML1,2, Peng H1,3, Lu Q1, Liu Q5, He HB5, Jiang TJ1, Lei MX1, Wan M2, Cao X2, Luo XH1.

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Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Department of Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha 410008, China.
Department of Orthopedic Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.


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.

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