Activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) is needed for the TGFβ-induced chondrogenic and osteogenic differentiation of mesenchymal stem cells

Biochem Biophys Res Commun. 2011 Feb 25;405(4):564-9. doi: 10.1016/j.bbrc.2011.01.068. Epub 2011 Jan 22.


The role of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway on the osteogenesis of progenitor and stem cells has received a lot of attention due to conflicting results in the literature. ERK1/2 has been reported to be both activating and inhibitory to the osteogenesis of different cell types under varying culture conditions. This study focused specifically on the role of ERK1/2 on the chondrogenesis and osteogenesis of mesenchymal stem cells (MSC) induced by cytokine exposure. Bone marrow-derived MSC were cultured in three-dimensional fibrin gel scaffolds and stimulated down the chondrogenic and osteogenic programs by addition of TGF-β3 to and osteogenic buffer media. Cells were cultured under control conditions (no cytokine supplementation), treated with TGF-β3 or treated with PD98059+TGF-β3 for 7 days. RT-PCR results show that addition of TGF-β3 significantly upregulates the phosphorylation of ERK1/2 and induces the cells down the chondrogenic and osteogenic pathways (as demonstrated by the significant upregulation of aggrecan, sox9, collagen types 1 & 2 gene expressions). Inhibition of ERK1/2 phosphorylation with PD98059 led to the abolishment of the upregulation of chondrogenic and osteogenic-specific gene expressions. These results demonstrate that ERK1/2 is needed for the chondrogenic and osteogenic differentiation of MSC as induced by TGF-β3 supplementation.

MeSH terms

  • Cells, Cultured
  • Chondrogenesis*
  • Enzyme Activation
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Osteogenesis*
  • Phosphorylation
  • Recombinant Proteins / pharmacology
  • Transforming Growth Factor beta3 / pharmacology


  • Recombinant Proteins
  • Transforming Growth Factor beta3
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3