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

作者：Arita Nestor A; Pelaez Daniel; Cheung Herman S^*

来源：Biochemical and Biophysical Research Communications, 2011, 405(4): 564-569.

DOI：10.1016/j.bbrc.2011.01.068

• Mesenchymal stem cells
• Chondrogenesis
• Osteogenesis
• MAPK

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 stern 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-beta 3 to and osteogenic buffer media. Cells were cultured under control conditions (no cytokine supplementation), treated with TGF-beta 3 or treated with PD98059 + TGF-beta 3 for 7 days. RT-PCR results show that addition of TGF-beta 3 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-beta 3 supplementation.

• 出版日期2011-2-25