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  • OCN is a marker of late stage osteogenic differentiation

    2018-10-22

    OCN is a marker of late stage osteogenic differentiation and regulates matrix mineralization during bone formation. VitD3 had the greatest positive effect on this transcript while Dex had the greatest negative effect. This effect has previously been documented for VitD3 supplemented osteoblast cultures (Viereck et al., 2002), however not for hPDCs. Interestingly, Dex again has a negative effect on the expression of this gene indicating that perhaps the role of Dex is in early augmentation of differentiation and the effect on late differentiation is negative. This hypothesis is substantiated through reports that Dex can attenuate VitD3 induced OCN expression (Schepmoes et al., 1991). Indeed it has been reported that the main effect of Dex on osteoblasts is through the modulation of 17-DMAG regulatory elements such as increased p27kip1 and decreased p21waf1/cip1 levels. The attenuation of osteoblast growth to high density by Dex is associated with severe impairment of mineralized extracellular matrix formation (Smith et al., 2000), however this may also be related to the timing cellular stimulation with Dex (McCulloch and Tenenbaum, 1986). Additionally, although VitD3 has the largest positive effect on OCN expression a smaller, but significant, positive effect is observed with the interaction of Dex&FBS. This may be due to the positive effect of the Dex&FBS interaction on Runx2 expression as OCN is a direct target of this transcription factor (Frendo et al., 1998).
    Materials and methods
    Acknowledgments The authors are grateful to Carla Geeroms, Isabelle De Wit and Kathleen Bosmans for the excellent technical assistance. This work is part of Prometheus, the Leuven Research & Development Division of Skeletal Tissue Engineering of the Katholieke Universiteit Leuven: www.kuleuven.be/prometheus. Funding for this research was obtained from the KULeuven — IOF Knowledge Platform ‘Prometheus’IOFKP/07/004.
    Introduction Pluripotent embryonic stem (ES) cells are an attractive source for deriving mature cell types required for a multitude of cell therapy applications. Extensive research has been invested to design protocols for driving ES cell differentiation to a single cell type. However, the phenotypic output of cell differentiation is influenced not only by the conditions used to induce differentiation but also by the phenotype of the starting cells. The starting population of undifferentiated human ES cells is critical as it has the potential to bias the differentiation of cells to, or away from the desired phenotype. During the maintenance of human ES cell lines, spontaneously differentiated cells are commonly found at colony boundaries. Spontaneous differentiation of cells is a source for cell heterogeneity in ES cell cultures and varying degrees of spontaneous differentiation are likely to be a significant source of passage-to-passage variability in ES cell studies, contributing to the difficulty of generating reproducible results. However, a subtle form of heterogeneity exists within the stem cell compartment itself. Heterogeneity has been identified in mouse ES cultures with respect to the expression of Nanog and Stella. For example, Nanog positive and negative mouse ES cells are interconvertible though Nanog−/− ES cells are more predisposed to differentiate (Chambers et al., 2007). Fluctuating levels of Stella expression have also been proposed to represent a dynamic equilibrium within mouse ES cultures, representing cells of either the inner cell mass or epiblast (Hayashi et al., 2008). Differential Stella expression marks functionally distinct cells: Stella negative cells were found to be permissive for differentiation to the trophectoderm lineage whereas Stella positive cells were not. It has been reported that during early stages of human ES cell differentiation genes associated with the pluripotent state are co-expressed with lineage specific transcription factors (Laslett et al., 2007). Such an observation may represent the existence of functionally distinct subsets of undifferentiated human ES cells but the relationship of these cells to differentiation potential has not yet been established.