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

• Published in: Cell death & disease Vol. 13; no. 5; pp. 494 - 13
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.05.2022; Springer Nature B.V; Nature Publishing Group
• Subjects: 13/31; 14/19; 38/39; 631/80/509; 64/110; 64/60; 692/699/2743/316/801; Aging; Aging - genetics; Angiogenesis; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; Bone growth; Bone loss; Bone mass; Cell Biology; Cell Culture; Endothelial cells; Endothelial Cells - metabolism; Endothelium; Immunology; Life Sciences; Mice; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neovascularization, Pathologic; Osteogenesis; Osteogenesis - genetics; Regeneration; Therapeutic targets
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-022-04902-w

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.