Abstract:The capacity of mesenchymal stem cells (MSCs) to differentiate into functional osteoblasts is tightly controlled by transcription factors that trigger osteoblast commitment and differentiation. The role of Twist1, a basic helix-loop-helix (bHLH) transcription factor, in osteogenic differentiation of MSCs remains unclear. Here we investigated the role of Twist1 in the osteogenic differentiation program of murine C3H10T1/2 mesenchymal cells. We showed that molecular silencing of Twist1 using short hairpin RNA (s… Show more
“…In cultured murine mesenchymal stem cells, we showed that Twist1 silencing reduces adipocyte gene expression and differentiation, although the mechanisms involved appear to be indirect. We found that Twist1 silencing increases FGF Receptor 2 (FGFR2) signaling (Miraoui et al, 2010). This results in reduction in adipocyte differentiation (Miraoui et al, 2010) because FGFR2 negatively controls adipocyte differentiation in murine mesenchymal stem cells (Miraoui et al, 2009).…”
Section: Role Of Twist1 In Chondrogenic and Adipogenic Differentiationmentioning
“…In cultured murine mesenchymal stem cells, we showed that Twist1 silencing reduces adipocyte gene expression and differentiation, although the mechanisms involved appear to be indirect. We found that Twist1 silencing increases FGF Receptor 2 (FGFR2) signaling (Miraoui et al, 2010). This results in reduction in adipocyte differentiation (Miraoui et al, 2010) because FGFR2 negatively controls adipocyte differentiation in murine mesenchymal stem cells (Miraoui et al, 2009).…”
Section: Role Of Twist1 In Chondrogenic and Adipogenic Differentiationmentioning
“…FGFR2 also plays an important role in osteoblastogenesis. In mesenchymal cells, constitutive Fgfr2 activation results in increased osteoblast differentiation and decreased adipocyte differentiation through ERK1/2 and PKCα signaling, resulting in increased Runx2 expression (Miraoui et al 2009(Miraoui et al , 2010b. Consistently, mice conditionally lacking Fgfr2 or harboring a mutation in Fgfr2c, the mesenchymal splice variant of Fgfr2, show decreased Runx2 expression, retarded ossification, and decreased bone mineral density, suggesting that Fgfr2 is a positive regulator of osteoblast maturation (Eswarakumar et al 2002;Yu et al 2003).…”
Section: Fgf/fgfr Signaling In Osteoblastogenesismentioning
Fibroblast growth factor (FGF) signaling pathways are essential regulators of vertebrate skeletal development. FGF signaling regulates development of the limb bud and formation of the mesenchymal condensation and has key roles in regulating chondrogenesis, osteogenesis, and bone and mineral homeostasis. This review updates our review on FGFs in skeletal development published in Genes & Development in 2002, examines progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis, and explores the mechanisms by which mutations in FGF signaling molecules cause skeletal malformations in humans. Links between FGF signaling pathways and other interacting pathways that are critical for skeletal development and could be exploited to treat genetic diseases and repair bone are also explored.
“…Conversely, Twist-1 overexpression inhibits osteogenesis without affecting Runx2 expression, 42 whereas Twist-1 silencing enhances osteogenesis of MSCs. 43 Further molecular analysis shows that Twist directly binds to the Runt DNA-binding domain of Runx2 to decrease binding of Runx2 to DNA. 38 These data show that Twist determines the onset of osteogenesis as an antagonist of Runx2.…”
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