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.
A novel conjugated oligomer (Co‐imiPhenTPE) based on 4‐(1H‐imidazo[4,5‐f][1,10]phenanthroline (imiPhen) and tetraphenylethene (TPE) moieties has been synthesized. The Co‐imiPhenTPE showed Zn2+‐induced aggregation induced emission enhancement (AIEE) with high selectivity. Moreover, the Zn2+‐Co‐imiPhenTPE complex exhibited a significant blue shift from 502 nm to 393 nm (109 nm) in ethanol/water (v/v=1 : 1). The transmission electron microscopy (TEM) measurements indicated that the thin sheet porous Co‐imiPhenTPE was evenly dispersed into approximate spherical nanoparticles after the addition of Zn2+. The approach may provide insights for designing large blue‐shifted fluorescent sensors.
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