miR-188-3p targets skeletal endothelium coupling of angiogenesis and osteogenesis during ageing

• DOI: 10.1038/s41419-022-04902-w
• Publication Date: 2022-05-25T03:51:44Z
• Authors: Wen-Zhen He; Mi Yang; Yangzi Jiang; Chen He; Yu-Chen Sun; Ling Liu; Mei Huang; Yu-Rui Jiao; Kai-Xuan Chen; Jing Hou; Min Huang; Yi-Li Xu; Xu Feng; Ya Liu; Qi Guo; Hui Peng; Yan Huang; Tian Su; Ye Xiao; Yusheng Li; Chao Zeng; Guanghua Lei; Xiang-Hang Luo; Chang-Jun Li
• Keywords: 0301 basic medicine; Aging; QH573-671; Neovascularization, Pathologic; Endothelial Cells; Article; Mice; MicroRNAs; 03 medical and health sciences; Osteogenesis; Animals; Endothelium; Cytology

AbstractA 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.