References of "Luyten, Frank"
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See detailIn silico screening to predict chondrocyte hypertrophy using a semiquantitative gene network model
Kerkhofs, Johan ULg; Leijten, Jeroen; Luyten, Frank et al

Poster (2015, April 30)

PURPOSE: In development, chondrocyte hypertrophy is a crucial and well-studied step in endochondral ossification. Hypertrophy may also play a role in pathophysiological processes, including osteoarthritis ... [more ▼]

PURPOSE: In development, chondrocyte hypertrophy is a crucial and well-studied step in endochondral ossification. Hypertrophy may also play a role in pathophysiological processes, including osteoarthritis. We employ a computational approach to estimate the effect of individual factors in this complex process. METHODS: We have combined information gleaned from a high number of publications on chondrocyte differentiation into a gene regulatory network of 46 factors and over 150 interactions. This network can estimate the stability of proliferative chondrocytes/permanent cartilage (stable state with SOX9 activity) and hypertrophic chondrocytes (stable state with RUNX2 activity) by employing 2 measures. A first measure is a Monte Carlo analysis that assesses stability in the face of random initial conditions, the second modifies stable states to estimate the sensitivity to perturbation. RESULTS: For each factor, these qualitative measures are calculated in silico under knockout and overexpression conditions and compared to the wild type situation. This enables screening of the effects of all incorporated factors on cartilage homeostasis, differentiation and pathogenesis via the initiation of hypertrophy. Indeed, our gene network analysis indicated multiple candidate genes for the development of osteoarthritis. Factors that amplify the SOX9 attractor basin include TGFβ, PPR, IGF-I, and PKA. The presence of RAS, IHH, GLI2 and FGF is required for the Runx2 stable state. Using a literature study, we corroborated several of the proposed factors. CONCLUSIONS: In silico screening of overexpression and knockout presents a novel strategy to improve bone and cartilage tissue engineering approaches, and can be used to propose a list of putative therapeutic targets for e.g. osteoarthritis. [less ▲]

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See detailIn vitro and in vivo comparative study of material properties crucial for reverse engineering of calcium phosphate scaffolds
Chai, Yoke Chin; Kerckhofs, Greet ULg; Bertels, Jeroen et al

Conference (2013)

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See detail3D perfusion bioreactor culture of human periosteum derived stem cells for bone tissue engineering
Sonnaert, Maarten; Papantoniou, Ioannis; Bloemen, Veerle et al

Conference (2013)

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See detailMicro-CT for first line screening of the scaffold material-, cell-and donor-variability on the ectopic bone forming capacity of tissue engineering constructs
Geeroms, Carla; Roberts, Scott; Van Hove, Astrid et al

Conference (2013)

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Peer Reviewed
See detailOptimised contrast enhanced nanoCT for volumetric analyses of in vitro manufactured tissue-engineered bone constructs
Sonnaert, Maarten; Kerckhofs, Greet ULg; Papantoniou, Ioannis et al

Conference (2013)

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See detailContrast enhanced nanoCT for volumetric analyses of in vitro manufactured tissue-engineered bone constructs: a soft tissue case study
Sonnaert, Maarten; Papantoniou, Ioannis; Geris, Liesbet ULg et al

Conference (2013)

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See detailContrast enhanced nanoCT for 3D quantitative and spatial analysis of in vitro manufactured extracellular matrix in metallic tissue engineering scaffolds
Sonnaert, Maarten; Papantoniou, Ioannis; Geris, Liesbet ULg et al

in Abstract book User Meeting Bruker MicroCT 2013 (2013)

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See detailMicro-CT evaluation of the effect of material, donor and implantation site variability on the bone forming capacity of progenitor cell/CaP-collagen constructs implanted ectopically in nude mice
Van Hove, Astrid; Geeroms, Carla; Maréchal, Marina et al

in Abstract book User Meeting Bruker MicroCT 2013 (2013)

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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 detailMicro-CT: a powerful tool for the characterization and evaluation of the bone formatting capacity of calcium phosphate–stem cells tissue engineering constructs
Kerckhofs, Greet ULg; Roberts, Scott J.; Wevers, Martine et al

in Abstract book SkyScan User Meeting 2011 (2011)

Detailed reference viewed: 4 (0 ULg)