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.
Highlights
A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31hiEmcnhi), is identified as coupling angiogenesis and osteogenesis
To determine the role of miRNAs in type H vessel generation, CD31hiEmcnhi and CD31loEmcnlo endothelial cells were sorted by fluorescence-activated cell sorting (FACS) from bone marrow cells of 1-month-old C57BL/6 mice to identify dysregulated miRNAs by performing miRNA microarray analysis
The higher level of miR-497B195 cluster expression in CD31hiEmcnhi endothelial cells was further confirmed by quantitative real-time PCR
Summary
A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31hiEmcnhi), is identified as coupling angiogenesis and osteogenesis. A specific endothelium was identified in murine skeletal system that is strongly positive for CD31 and endomucin with signalling properties that support bone formation and regeneration[5,6]. This new capillary type is named CD31hiEmcnhi or type H vessels and able to mediate perivascular osteoprogenitors differentiation and couple angiogenesis to osteogenesis[5]. Our study provides an important mechanism of miRNA regulating angiogenesis during coupling with osteogenesis
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