miR-188-3p targets skeletal endothelium coupling of angiogenesis and osteogenesis during ageing.
miR-188-3p targets skeletal endothelium coupling of angiogenesis and osteogenesis during ageing.
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miR-188-3p靶向衰老过程中血管生成和骨生成的骨骼内皮偶联
DOI：
10.1038/s41419-022-04902-w
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发表时间：
2022-05-25
影响因子：
9
通讯作者：
Li, Chang-Jun
中科院分区：
文献类型：
--
作者：
He, Wen-Zhen;Yang, Mi;Jiang, Yangzi;He, Chen;Sun, Yu-Chen;Liu, Ling;Huang, Mei;Jiao, Yu-Rui;Chen, Kai-Xuan;Hou, Jing;Huang, Min;Xu, Yi-Li;Feng, Xu;Liu, Ya;Guo, Qi;Peng, Hui;Huang, Yan;Su, Tian;Xiao, Ye;Li, Yusheng;Zeng, Chao;Lei, Guanghua;Luo, Xiang-Hang;Li, Chang-Jun
近年来发现一种特殊的骨毛细血管亚型，即H型血管，高表达CD 31和内粘蛋白，可偶联血管生成和成骨。骨组织中H型血管的数量随着年龄的增长而减少，这种减少的潜在机制尚不清楚。在这里，我们报告microRNA-188- 3 p（miR-188- 3 p）参与了这一过程。miRNA-188- 3 p在骨骼内皮中表达上调，并在衰老过程中负调节H型血管的形成。耗尽miR-188的小鼠显示H型血管中年龄相关性下降减轻。相反，内皮特异性过表达miR-188- 3 p减少了H型血管的数量，导致骨量减少和骨再生延迟。从机制上讲，我们发现miR-188通过直接靶向内皮细胞中的整合素β3来抑制H型血管形成。我们的研究结果表明，miR-188- 3 p是H型血管形成的关键调节因子，可能是预防骨丢失和加速骨再生的潜在治疗靶点。
A specific bone capillary subtype, namely type H vessels, with high expression of CD31 and endomucin, was shown to couple angiogenesis and osteogenesis recently. The number of type H vessels in bone tissue declines with age, and the underlying mechanism for this reduction is unclear. Here, we report that microRNA-188-3p (miR-188-3p) involves this process. miRNA-188-3p expression is upregulated in skeletal endothelium and negatively regulates the formation of type H vessels during ageing. Mice with depletion of miR-188 showed an alleviated age-related decline in type H vessels. In contrast, endothelial-specific overexpression of miR-188-3p reduced the number of type H vessels, leading to decreased bone mass and delayed bone regeneration. Mechanistically, we found that miR-188 inhibits type H vessel formation by directly targeting integrin β3 in endothelial cells. Our findings indicate that miR-188-3p is a key regulator of type H vessel formation and may be a potential therapeutic target for preventing bone loss and accelerating bone regeneration.
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影响因子：
7.5
作者：
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通讯作者：
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影响因子：
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通讯作者：
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