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Endothelial cells modulate osteogenesis in calcifying vascular cells.

Victoria Shin1, Amina F Zebboudj, Kristina Boström

  • 1Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Journal of Vascular Research
|March 20, 2004
PubMed
Summary

Endothelial cells (EC) influence vascular calcification. EC can inhibit calcification on collagen IV, but Matrix GLA protein (MGP) enhances it, revealing complex interactions in atherosclerosis.

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Area of Science:

  • Cardiovascular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The role of vascular endothelium in atherosclerotic calcification remains unclear.
  • Endothelial cells (EC) produce bone morphogenetic proteins (BMP) and exhibit osteoinductive properties.
  • Calcifying vascular cells (CVC) mineralize in vitro, serving as a model for vascular calcification.

Purpose of the Study:

  • To investigate the osteoinductive potential of EC on vascular cells.
  • To determine how EC influence CVC calcification and differentiation.
  • To explore the roles of collagen and Matrix GLA protein (MGP) in EC-CVC interactions.

Main Methods:

  • A coculture model was established with EC and CVC on collagen I or IV.
  • Nodule formation, calcification, and expression of osteogenic/chondrogenic markers were assessed.

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  • The effects of MGP, noggin (a BMP inhibitor), and BMP-2 were evaluated.

    • Main Results:

    • On collagen IV, EC inhibited CVC calcification and marker expression, suggesting dedifferentiation.
    • MGP enhanced Cbfa1 expression and calcification in CVC, particularly on collagen IV.
    • EC's effect on calcification was inhibited by noggin and mimicked by BMP-2.

    Conclusions:

    • Endothelium plays a significant role in vascular calcification.
    • Collagen type and MGP modulate EC-mediated vascular calcification.
    • Nodule formation and cell differentiation are distinct processes influenced by EC and MGP.