A comparison of the involvement of p38, ERK1/2 and PI3K in growth factor-induced chondrogenic differentiation of mesenchymal stem cells

• Published in: Biochemical and biophysical research communications 2008-04, Vol.368 (4), p.990-995
• Main Authors: McMahon, Louise A., Prendergast, Patrick J., Campbell, Veronica A.
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation - physiology; Chondrogenesis - physiology; Chondrogenic differentiation; Collagen-GAG scaffold; IGF-1; Insulin-Like Growth Factor I - physiology; Male; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mitogen-Activated Protein Kinase 1 - physiology; Mitogen-Activated Protein Kinase 3 - physiology; p38; p38 Mitogen-Activated Protein Kinases - physiology; Phosphatidylinositol 3-Kinases - physiology; PI3K; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Wistar; TGF-β1; Transforming Growth Factor beta1 - physiology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.01.160

Adult mesenchymal stem cells (MSCs) are under investigation as an alternative cell source for the engineering of cartilage tissue in three-dimensional (3D) scaffolds. However, little is known about the intracellular mechanisms involved in the chondrogenic differentiation of MSCs. This study investigated the signaling pathways evoked by TGF-β1 and IGF-1 that mediated chondrogenic differentiation in adult rat bone-marrow derived MSCs in (i) monolayer on plastic and (ii) a 3D collagen-GAG scaffold. The data demonstrated involvement of the p38 pathway, but not ERK1/2 or PI3K in TGF-β1-induced chondrogenic differentiation in monolayer. Similarly, when the MSCs were seeded onto a collagen-GAG scaffold and treated with TGF-β1, the chondrogenic differentiation was dependent upon p38. In contrast, IGF-1-induced chondrogenic differentiation in monolayer involved p38, ERK1/2, as well as PI3K. The phosphorylation of Akt occurred downstream of PI3K and phospho-Akt was found to accumulate in the nucleus of IGF-1-treated cells. When MSCs were seeded onto the collagen-GAG scaffold and exposed to IGF-1, PI3K was required for chondrogenesis. These findings highlight the respective and differential involvement of p38, ERK1/2 and PI3K in growth factor-induced chondrogenesis of MSCs and demonstrates that intracellular signaling pathways are similar when differentiation is stimulated in a 2D or 3D environment.