Poster (Scientific congresses and symposiums)
In silico screening to predict chondrocyte hypertrophy using a semiquantitative gene network model
Kerkhofs, Johan; Leijten, Jeroen; Luyten, Frank et al.
2015OARSI 2015
 

Files


Full Text
oarsi 2015 abstract in silico screening of hypertrophy_rvJL.docx
Author preprint (16.62 kB)
Download

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
hypertrophy; gene network; modelling
Abstract :
[en] 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.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
Kerkhofs, Johan ;  Université de Liège - ULiège > Form. doct. sc. ingé. (aérosp. & méca - Bologne)
Leijten, Jeroen
Luyten, Frank
Geris, Liesbet  ;  Université de Liège > Département d'aérospatiale et mécanique > Génie biomécanique
Language :
English
Title :
In silico screening to predict chondrocyte hypertrophy using a semiquantitative gene network model
Publication date :
30 April 2015
Event name :
OARSI 2015
Event date :
30-04-2015 to 03-05-2015
European Projects :
FP7 - 279100 - BRIDGE - Biomimetic process design for tissue regeneration: from bench to bedside via in silico modelling
Funders :
CE - Commission Européenne [BE]
Available on ORBi :
since 22 June 2015

Statistics


Number of views
51 (2 by ULiège)
Number of downloads
31 (2 by ULiège)

Bibliography


Similar publications



Contact ORBi