Endothelial progenitor cell‑derived extracellular vesicle‑meditated cell‑to‑cell communication regulates the proliferation and osteoblastic differentiation of bone mesenchymal stromal cells

Mol Med Rep. 2017 Nov;16(5):7018-7024. doi: 10.3892/mmr.2017.7403. Epub 2017 Aug 31.

Abstract

Bone tissue engineering is a promising treatment strategy to increase bone regeneration. Endothelial progenitor cells (EPCs) and bone marrow stromal cells (BMSCs) are commonly used to promote vessel formation and osteoblastic differentiation in tissue engineering. Previous studies have demonstrated that EPCs regulate both proliferation and differentiation of BMSCs. However, the underlying mechanism remains unclear. Understanding this mechanism is critical to developing more effective treatments. The role of extracellular vesicles in cell‑to‑cell communication has attracted substantial attention. These small vesicles deliver proteins, DNA, and RNA and consequently regulate the commitment, function, and differentiation of target cells. In the present study, EPC‑derived extracellular vesicles (EPC‑EVs were isolated using gradient ultracentrifugation and ultrafiltration and the influence of EPC‑EVs on BMSC osteoblastic differentiation and proliferation was examined in vitro. The results indicated that EPC‑EVs regulate the osteoblastic differentiation of BMSCs by inhibiting the expression of osteogenic genes and increasing proliferation in vitro. It is suggested that the results regarding the role of EPC‑EVs will provide a novel way to explain the crosstalk between EPCs and BMSCs.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Cell Communication*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Culture Media, Conditioned / pharmacology
  • Endothelial Progenitor Cells / cytology
  • Endothelial Progenitor Cells / metabolism
  • Extracellular Vesicles / physiology*
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Osteocalcin / metabolism
  • Osteogenesis* / drug effects
  • Tetraspanin 30 / metabolism

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Culture Media, Conditioned
  • Tetraspanin 30
  • Osteocalcin