miR-188-3p targets skeletal endothelium coupling of angiogenesis and osteogenesis during ageing
Wenzhen He, Mi Yang, Yangzi Jiang, Chen He, Yuchen Sun, Ling Liu, Mei Huang, Yurui Jiao, Kaixuan Chen, Jing Hou, Min Huang, Yili Xu, Feng Xu, Ya Liu, Qi Guo, Hui Peng, Yan Huang, Tian Su, Ye Xiao, Yusheng Li, Chao Zeng, Guanghua Lei, Xiang‐Hang Luo, Changjun Li
Abstract
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.