Mechanical Stress Regulates Osteogenesis and Adipogenesis of Rat Mesenchymal Stem Cells through PI3K/Akt/GSK-3β/β-Catenin Signaling Pathway

Abstract

Osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) are regarded as being of great importance in the regulation of bone remodeling. In this study, rat BMSCs were exposed to different levels of cyclic mechanical stress generated by liquid drops and cultured in general medium or adipogenic medium. Markers of osteogenic (Runx2 and Collagen I) and adipogenic (C/EBPα, PPARγ, and lipid droplets) differentiation were detected using Western blot and histological staining. The protein levels of members of the phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase 3β (GSK-3β)/β-catenin signaling pathway were also examined. Results showed that small-magnitude stress significantly upregulated Runx2 and Collagen I and downregulated PPARγ and C/EBPα expression in BMSCs cultured in adipogenic medium, while large-magnitude stress reversed the effect when compared with unloading groups. The PI3K/Akt signaling pathway could be strongly activated by mechanical stimulation; however, large-magnitude stress led to decreased activation of the signaling pathway when compared with small-magnitude stress. Activation of β-catenin with LiCl led to increased expression of Runx2 and Collagen I and reduction of C/EBPα and PPARγ expression in BMSCs. Inhibition of PI3K/Akt signaling partially blocked the expression of β-catenin. Taken together, our results indicate that mechanical stress-regulated osteogenesis and adipogenesis of rat BMSCs are mediated, at least in part, by the PI3K/Akt/GSK-3β/β-catenin signaling pathway.

Osteogenic cellular activity around onlaid octacalcium phosphate‐gelatin composite onto rat calvaria

“…6). However, the expression was significantly higher in first area than that in second area in OCP/Gel with PTFE, suggesting that the second area in OCP/Gel with PTFE may still be in a state that new bone could actively be being formed through the mechanical stress condition as reported previously 47 and as shown in fact in the extent of bone augmentation (Fig. However, the expression was significantly higher in first area than that in second area in OCP/Gel with PTFE, suggesting that the second area in OCP/Gel with PTFE may still be in a state that new bone could actively be being formed through the mechanical stress condition as reported previously 47 and as shown in fact in the extent of bone augmentation (Fig.…”

Weighted gene correlation network analysis reveals novel biomarkers associated with mesenchymal stromal cell differentiation in early phase

“…The RAS regulated ossification and angiogenesis of bones, as well as OS differentiation (Durik, Sevá Pessôa & Roks, 2012). On the other hand, the phosphatidylinositol signaling system could regulate the OS and AD differentiation of bone marrow MSCs (Song et al, 2017). SGK1 is a member of the PI3-kinase pathway, which regulates cell survival, proliferation and differentiation (Lang et al, 2006).…”

Gene Expression Profiling of Human Adipose Tissue Stem Cells during 2D versus 3D Adipogenesis

“…Generally, PI3K-AKT (Fig. 4b) is downstream of integrin signaling regulating MSC differentiation to early osteogenesis or adipogenesis in a context-or time-dependent DOI: 10.1159/000507187 manner [Song et al, 2017]. During adipogenic differentiation, the mediators of the PI3K-AKT pathway and its downstream effectors mTOR, p27, FOXO1, and p70S6K are increased [Ramazzotti et al, 2019].…”