Cell Death and Disease (May 2022)

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

  • 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

DOI
https://doi.org/10.1038/s41419-022-04902-w
Journal volume & issue
Vol. 13, no. 5
pp. 1 – 13

Abstract

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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.