MiR-497∼195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch and HIF-1α activity.
MiR-497∼195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch and HIF-1α activity.
复制标题
DOI：
10.1038/ncomms16003
复制
发表时间：
2017-07-07
影响因子：
16.6
通讯作者：
Luo XH
中科院分区：
文献类型：
--
作者：
Yang M;Li CJ;Sun X;Guo Q;Xiao Y;Su T;Tu ML;Peng H;Lu Q;Liu Q;He HB;Jiang TJ;Lei MX;Wan M;Cao X;Luo XH
一种特殊的骨血管亚型，CD31和内粘蛋白(CD31hiEmcnhi)强阳性，被鉴定为耦合血管生成和成骨。CD31hiEmcnhi型血管的丰度随着年龄的增长而减少。在这里，我们发现miR-497CD195簇在∼内皮细胞中的表达很高，但随着年龄的增长逐渐减少。内皮细胞中miR-497CD195缺失的小鼠表现出较少的∼血管和较低的骨量。相反，在小鼠内皮细胞中过表达miR-497CD31hiCD195可以缓解与年龄相关的∼31hiEmcnhi血管减少和骨丢失。MIR-497HIF195簇通过分别靶向F-box和WD-40结构域蛋白(Fbxw7)和具有跨膜结构域的Pro-4-羟基酶(P4HTM)来维持内皮细胞∼活性和α稳定性。值得注意的是，通过静脉注射适配子-agomiR-195对miR-195进行内皮特异性激活，可以刺激老年小鼠的CD31hiEmcnhi血管和骨形成。综上所述，我们的研究表明，MIR-497MER195调控血管生成和成骨，可能成为治疗老年性骨质疏松症的潜在靶点。H型内皮由CD31和Endomucin的高表达所定义，存在于骨骼中，促进血管生成和成骨。在这里，杨等人。结果表明，miR-497HIF 195簇通过控制∼调节器Fbxw7和HIF调节器P4HTM的水平来调节H型内皮细胞的生成和维持。
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. H-type endothelium, defined by the high expression of CD31 and endomucin, is found in the bone where it promotes angiogenesis and osteogensis. Here Yang et al. show that the miR-497∼195 cluster regulates the generation and maintenance of the H-type endothelium by controlling the levels of Notch regulator Fbxw7 and the HIF regulator P4HTM.
登录
查看更多内容
影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
MicroRNA 在破骨细胞和骨质疏松症中的作用
影响因子：
4.1
作者：
Tang P;Xiong Q;Ge W;Zhang L
通讯作者：
Zhang L
影响因子：
14.8
作者：
Kusumbe，Anjali P.;Ramasamy，Saravana K.;Adams，Ralf H.
通讯作者：
Adams，Ralf H.
影响因子：
25
作者：
Hoeck, Joerg D.;Jandke, Anett;Behrens, Axel
通讯作者：
Behrens, Axel
影响因子：
64.8
作者：
Kusumbe AP;Ramasamy SK;Adams RH
通讯作者：
Adams RH