DLL1/NOTCH1 signaling pathway maintain angiogenesis in meniscus development and degeneration

Int J Biochem Cell Biol. 2024 Jul:172:106589. doi: 10.1016/j.biocel.2024.106589. Epub 2024 May 19.

Abstract

Objectives: The decline in vascular capacity within the meniscus is a well-documented phenomenon during both development and degeneration. Maintaining vascular integrity has been proposed as a potential therapeutic strategy for osteoarthritis. Therefore, our study aims to investigate the characteristics of endothelial cells and blood vessels in embryonic and degenerated meniscus tissues.

Methods: Human embryonic and mature menisci were used for histological analyses. Single-cell RNA sequencing was used to identify cell clusters and their significant genes in embryo meniscus to uncover characteristic of endothelial cells. Computer analysis and various staining techniques were used to characterize vessels in development and osteoarthritis meniscus.

Results: Vessels structure first observed in E12w and increasing in E14w. Vessels were veins majorly and arteries growth in E35w. Endothelial cells located not only perivascular but also in the surface of meniscus. The expression of DLL1 was observed to be significantly altered in endothelial cells within the vascular network that failed to form. Meniscus tissues affected by osteoarthritis, characterized by diminished vascular capacity, displayed reduced levels of DLL1 expression. Experiment in vitro confirmed DLL1/NOTCH1 be vital to angiogenesis.

Conclusion: Lack of DLL1/NOTCH1 signaling pathway was mechanism of vascular declination in development and degenerated meniscus.

Keywords: Angiogenesis; Development; Meniscus; NOTCH signaling.

MeSH terms

  • Angiogenesis
  • Calcium-Binding Proteins* / genetics
  • Calcium-Binding Proteins* / metabolism
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Meniscus / metabolism
  • Meniscus / pathology
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Physiologic
  • Osteoarthritis* / genetics
  • Osteoarthritis* / metabolism
  • Osteoarthritis* / pathology
  • Receptor, Notch1* / genetics
  • Receptor, Notch1* / metabolism
  • Signal Transduction*

Substances

  • Receptor, Notch1
  • NOTCH1 protein, human
  • Calcium-Binding Proteins
  • DLK1 protein, human
  • Membrane Proteins
  • Intercellular Signaling Peptides and Proteins