AICAR, a small chemical molecule, primes osteogenic differentiation of adult mesenchymal stem cells

Int J Artif Organs. 2011 Dec;34(12):1128-36. doi: 10.5301/ijao.5000007.

Abstract

The chemical approach to controlling stem cell fates is emerging as a powerful tool, holding great promise in tissue engineering and regenerative medicine. Various small molecules have been demonstrated capable of modulating stem cell differentiation. In this paper, we studied the effects of 5-aminoimidazole-4-carboxamide-1-ß-riboside (AICAR), an activator of AMP-activated protein kinase (AMPK), on mesenchymal stem cells (MSCs). AICAR at high concentrations (1.0-2.0 mM) significantly inhibited proliferation of both human amnion-derived MSCs (hAMSCs) and rabbit bone marrow-derived MSCs (BM-MSCs). Most importantly, AICAR efficiently promoted the osteogenic differentiation of hAMSCs and BM-MSCs in both growth medium and osteogenic medium. However, Metformin, another AMPK activator, showed no such effects. Meanwhile, AICAR significantly inhibited adipogenic differentiation of hAMSCs and BM-MSCs. Our data suggests that AICAR represents a potent molecule, which can be applied in bone tissue regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adipogenesis / drug effects
  • Adult Stem Cells / drug effects*
  • Adult Stem Cells / metabolism
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Humans
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Metformin / pharmacology
  • Osteogenesis / drug effects*
  • Rabbits
  • Ribonucleotides / pharmacology*
  • Time Factors

Substances

  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Metformin
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide