27-Hydroxycholesterol Negatively Affects the Function of Bone Marrow Endothelial Cells in the Bone Marrow

Int J Mol Sci. 2024 Sep 29;25(19):10517. doi: 10.3390/ijms251910517.

Abstract

Hematopoietic stem cells (HSCs) reside in specific microenvironments that facilitate their regulation through both internal mechanisms and external cues. Bone marrow endothelial cells (BMECs), which are found in one of these microenvironments, play a vital role in controlling the self-renewal and differentiation of HSCs during hematological stress. We previously showed that 27-hydroxycholesterol (27HC) administration of exogenous 27HC negatively affected the population of HSCs and progenitor cells by increasing the reactive oxygen species levels in the bone marrow. However, the effect of 27HC on BMECs is unclear. To determine the function of 27HC in BMECs, we employed magnetic-activated cell sorting to isolate CD31+ BMECs and CD31- cells. We demonstrated the effect of 27HC on CD31+ BMECs and HSCs. Treatment with exogenous 27HC led to a decrease in the number of BMECs and reduced the expression of adhesion molecules that are crucial for maintaining HSCs. Our results demonstrate that BMECs are sensitively affected by 27HC and are crucial for HSC survival.

Keywords: 27-hydroxycholesterol; bone marrow endothelial cell; hematopoietic stem cell.

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Bone Marrow / metabolism
  • Bone Marrow Cells* / cytology
  • Bone Marrow Cells* / drug effects
  • Bone Marrow Cells* / metabolism
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Endothelial Cells* / drug effects
  • Endothelial Cells* / metabolism
  • Hematopoietic Stem Cells* / cytology
  • Hematopoietic Stem Cells* / drug effects
  • Hematopoietic Stem Cells* / metabolism
  • Hydroxycholesterols* / metabolism
  • Hydroxycholesterols* / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Hydroxycholesterols
  • 27-hydroxycholesterol
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Reactive Oxygen Species