Abstract
The standard procedure for the osteogenic differentiation of multipotent stem cells is treatment of a confluent monolayer with a cocktail of dexamethasone (Dex), ascorbic acid (Asc) and β-glycerophosphate (β-Gly). This review describes the effects of these substances on intracellular signaling cascades that lead to osteogenic differentiation of bone marrow stroma-derived stem cells. We conclude that Dex induces Runx2 expression by FHL2/β-catenin-mediated transcriptional activation and that Dex enhances Runx2 activity by upregulation of TAZ and MKP1. Asc leads to the increased secretion of collagen type I (Col1), which in turn leads to increased Col1/α2β1 integrin-mediated intracellular signaling. The phosphate from β-Gly serves as a source for the phosphate in hydroxylapatite and in addition influences intracellular signaling molecules. In this context we give special attention to the differences between dystrophic and bone-specific mineralization.
Highlights
Osteogenic differentiation protocols using dexamethasone (Dex), ascorbic acid (Asc) and β-glycerophosphate (β-Gly) are frequently used for many experimental approaches, including tissue engineering approaches or the approval of differentiation capabilities of particular cell types
We describe the latest findings concerning the underlying mechanisms involved in osteogenic differentiation of Bone marrow stromal cell (BMSC) cultures under the influence of Dex, Ascorbic acid (Asc) and β-Gly
In addition to the ERKmediated increase in BMP2 expression, Tada and colleagues [52] demonstrated that Inorganic phosphate (Pi) increases BMP2 expression by activation of the cyclic-AMP/proteinkinase-A pathway. They demonstrated that both pathways operate independently of each other. It appears that FHL2 is a crucial factor in the osteogenic commitment of BMSCs and that the key event by which Dex induces osteogenesis is the upregulation of FHL2 expression
Summary
Osteogenic differentiation protocols using dexamethasone (Dex), ascorbic acid (Asc) and β-glycerophosphate (β-Gly) are frequently used for many experimental approaches, including tissue engineering approaches or the approval of differentiation capabilities of particular cell types. They transfected rat dermal fibroblasts with Runx and found that only in combination with Dex was the expression of osteocalcin and bone sialo protein (BSP) induced, and mineral was deposited They ensured that this effect was not an artifact of the nonosteogenic cells but can be observed in primary BMSCs. It was found that the upregulation of MKP-1 results in the de-phosphorylation of serine 125 of Runx leading to enhanced Runx trans-activation. Interaction is provided by the finding that inhibition of BMP signaling disrupts the ability of Runx to stimulate osteoblast differentiation in mice, leading to the suggestion by Phimphilai and colleagues that autocrine BMP production is necessary for Runx activity in murine stem cells of the BMSC population [23]. They demonstrated that both pathways operate independently of each other
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