Article (Scientific journals)
Capturing the wide variety of impaired fracture healing phenotypes in Neurofibromatosis Type 1 with eight key factors: a computational study.
carlier, aurelie; brems, h.; ashbourn, j.m.a. et al.
2016In Scientific Reports, 7, p. 20010
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Abstract :
[en] Congenital pseudarthrosis of the tibia (CPT) is a rare disease which normally presents itself during early childhood by anterolateral bowing of the tibia and spontaneous tibial fractures. Although the exact etiology of CPT is highly debated, 40-80% of CPT patients are carriers of a mutation in the Neurofibromatosis Type 1 (NF1) gene, which can potentially result in an altered phenotype of the skeletal cells and impaired bone healing. In this study we use a computational model of bone regeneration to examine the effect of the Nf1 mutation on bone fracture healing by altering the parameter values of eight key factors which describe the aberrant cellular behaviour of Nf1 haploinsufficient and Nf1 bi-allelically inactivated cells. We show that the computational model is able to predict the formation of a hamartoma as well as a wide variety of CPT phenotypes through different combinations of altered parameter values. A sensitivity analysis by "Design of Experiments" identified the impaired endochondral ossification process and increased infiltration of fibroblastic cells as key contributors to the degree of severity of CPT. Hence, the computational model results have added credibility to the experimental hypothesis of a genetic cause (i.e. Nf1 mutation) for CPT.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
carlier, aurelie
brems, h.
ashbourn, j.m.a.
nica, i
legius, e
Geris, Liesbet  ;  Université de Liège > Département d'aérospatiale et mécanique > Génie biomécanique
Language :
English
Title :
Capturing the wide variety of impaired fracture healing phenotypes in Neurofibromatosis Type 1 with eight key factors: a computational study.
Publication date :
2016
Journal title :
Scientific Reports
eISSN :
2045-2322
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
7
Pages :
20010
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
FP7 - 279100 - BRIDGE - Biomimetic process design for tissue regeneration: from bench to bedside via in silico modelling
Funders :
CE - Commission Européenne [BE]
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