Abstract
Mesenchymal stem cells are fundamental for bone formation and repair since they respond to microenvironmental stimuli by undergoing osteogenic differentiation. We show that the kinase and cation channel TRPM7 and the magnesium transporter MagT1 have a role in harmonizing the osteogenic differentiation of human mesenchymal stem cells. TRPM7 and MagT1 are upregulated in osteogenic differentiation and silencing either one accelerates osteogenic differentiation, partly through the activation of autophagy. Intriguingly, similar results were obtained when the cells were cultured under magnesium deficient conditions. These results underpin the contribution of magnesium, TRPM7 and MagT1 to autophagy and osteoblastogenesis.
Highlights
The bone is a metabolically active tissue that is continuously remodeled in development and throughout life to repair microdamages and adjust its architecture to changing mechanical needs[1]
Western blot shows that both Transient Receptor Potential Melastatin 7 (TRPM7) and MagT1 are upregulated in human MSC (hMSC) exposed to the osteogenic medium for 6 and 14 days (Figs 1B and S1A,B)
To investigate the role of TRPM7 and MagT1 in the osteogenic differentiation of hMSC, we transiently transfected the cells with specific siRNAs for TRPM7, MagT1 or with a non-silencing siRNA as a control (−) and cultured hMSC in culture medium (CM) for 3 days
Summary
The bone is a metabolically active tissue that is continuously remodeled in development and throughout life to repair microdamages and adjust its architecture to changing mechanical needs[1]. Transient Receptor Potential Melastatin 7 (TRPM7), a dual-function kinase and cation channel, has been shown to mediate the osteogenic differentiation of murine MSC in response to shear stress[5]. In these cells TRPM7 directly senses membrane tension and is involved in mechanotransduction[6]. A recent report shows that Mg deprivation as well as mesendogen, an inhibitor of TRPM7, robustly enhance mesoderm and definitive endoderm differentiation of embryonic stem cells[14] On these bases, we investigated the expression and the role of TRPM7 and MagT1 in human MSC (hMSC) induced to differentiate into osteoblasts by exposure to an osteogenic cocktail. We evaluated the activation and the role of autophagy in hMSC after inhibiting the expression of MagT1 or TRPM7 or culturing the cells under Mg deficient conditions
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