References of "Eyckmans, jeroen"
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See detailThe Effect of Activating Fibroblast Growth Factor Receptor 3 Mutations on Osteogenic Differentiation and Ectopic Bone Formation by Human Periosteal Derived Cells
Bolander, Johanna; Roberts, Scott; Eyckmans, jeroen et al

in Journal of Tissue Science & Engineering (2012), 2

Activating mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) have previously been shown to cause skeletal dysplasias through their effect on growth plate chondrocytes. However, the effect of FGFR3 ... [more ▼]

Activating mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) have previously been shown to cause skeletal dysplasias through their effect on growth plate chondrocytes. However, the effect of FGFR3 mutations on bone progenitor cells may differ. The objective of this study was to investigate the effect of specific activating FGFR3 mutations on ectopic in vivo bone formation by periosteal derived cells (PDCs) seeded on calcium phosphate/ collagen scaffolds. PDCs were isolated from hypochondroplasic (N540K mutation) and achondroplasic (G380R mutation) patients, along with age/sex matched controls. These cells were characterised in vitro for proliferation, osteogenic differentiation, FGFR3 signalling and in vivo bone formation. Subsequently, empirical modelling was used to find correlations between in vivo formed bone and in vitro cell behaviour. These data showed that in contrast to the G380R mutation, which produced no bone, the N540K mutation induced significant ectopic bone formation on specific carriers. This allowed correlation between percentage of induced bone formation to elevated in vitro proliferation and differentiation. Correlating osteogenic markers included Collagen type 1, alkaline phosphatase and osteocalcin. Enhanced proliferation was attributed to increased phosphorylation of Erk-1/2. This study highlights the importance of FGFR3 in periosteal cell differentiation and also indicates it potential for targeted tissue engineering strategies. [less ▲]

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See detailCrosstalk Modeling of Wnt, BMP and ERK Pathways during osteochondrogenic differentiation
Geris, Liesbet ULg; Vandeput, Maarten; Roberts, Scott et al

in proceedings of the International Symposium on Biomechanics and Biology of Bone Regeneration “From Functional Assessment To Guided Tissue Formation (2009, November)

The in vitro engineering of tissues may be achieved by mimicking in vivo tissue development. Although multiple skeletal tissue engineering applications already exist, the underlying mechanisms at protein ... [more ▼]

The in vitro engineering of tissues may be achieved by mimicking in vivo tissue development. Although multiple skeletal tissue engineering applications already exist, the underlying mechanisms at protein level are often poorly understood. Growth factors and protein pathways precisely navigate mesenchymal stem cells trough the correct cascades. A detailed understanding of these cascades will enable us to develop efficient and robust production methods, which are required for large scale tissue engineering applications. Multiple studies hypothesize that the Wnt/β-catenin pathway acts as a switching mechanism to determine the differential fate of esenchymal cells in osteoblasts or chondrocytes during skeletogenesis. The concentration of β-catenin is a key factor in this mechanism. Wnt upregulates the productionof β-catenin which in turn upregulates Runx2 and downregulates Sox9. High concentrations of Runx2 relative to Sox9 lead to osteoblasts, while the opposite situation leads to chondrocytes. Crosstalks of the Wnt pathway with other pathways such as that of BMP and ERK expand the amount of factors that can influence β-catenin, turning the linear signaling cascade into a complex network with multiple starting conditions. A mathematical model was derived from literature describing the pathways of BMP, Wnt and ERK as well as various crosstalks between these pathways that were suggested in literature. CellDesigner™ was used to formulate, solve and visualize the Ordinary Differential Equations describing the temporal evolution of the various model constituents. Multiple starting conditions (various concentrations of BMP, Wnt and ERK) were examined to clarify the crosstalk effect. Modeling various crosstalks proposed in literature resulted in a mutual inhibitory effect between Wnt and BMP signaling, an effect independently described in literature. Experiments are ongoing to corroborate the model predictions. [less ▲]

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