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

Cell Death Dis. 2022 May 25;13(5):494. doi: 10.1038/s41419-022-04902-w.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Animals
  • Endothelial Cells / metabolism
  • Endothelium
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neovascularization, Pathologic
  • Osteogenesis* / genetics

Substances

  • MIRN188 microRNA, mouse
  • MicroRNAs