COMP-Ang1, a variant of angiopoietin 1, inhibits serum-deprived apoptosis of mesenchymal cells via PI3K/Akt and mitogen-activated protein kinase pathways

Pharmacology. 2010;86(5-6):327-35. doi: 10.1159/000321885. Epub 2010 Nov 29.

Abstract

Background/aims: Cartilage oligomeric matrix protein (COMP)-angiopoietin 1 (Ang1) is a soluble and stable form of Ang1 which plays important roles in vessel formation and the survival of endothelial cells, neurons and cardiomyocytes. However, the effects of COMP-Ang1 on the survival of mesenchymal cells are unknown. Mesenchymal cells have been transplanted with some scaffolds for bone tissue regeneration, but they occasionally underwent cell death due to a lack of nutrient supply. This study examined the effects of COMP-Ang1 on the survival of mesenchymal cells under nutrient-deprived conditions.

Methods: Primary and C3H10T1/2 mesenchymal cells were cultured under serum deprivation with or without COMP-Ang1. The effects of COMP-Ang1 on mesenchymal cell survival and its molecular mechanism were determined using a viability test, RT-PCR, Western blotting and fluorescence-activated cell sorting analysis.

Results and conclusion: COMP-Ang1 inhibited the nutrient-deprived apoptotic cell death of mesenchymal cells through the Akt, p38 and extracellular-signal-regulated kinase (ERK) pathways. In addition, COMP-Ang1 reversed the nutrient-deprived suppression of cyclin D1 mRNA expression. These results suggest that COMP-Ang1 has a protective role in the survival of nutrient-deprived mesenchymal cells. The use of COMP-Ang1 with some scaffolds might be useful for bone tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cyclin D1 / genetics
  • Humans
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphatidylinositol 3-Kinase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / metabolism
  • Recombinant Fusion Proteins / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • COMP-Ang1 fusion protein
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Cyclin D1
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases