Article (Scientific journals)
Early BMP, Wnt and Ca(2+)/PKC pathway activation predicts the bone forming capacity of periosteal cells in combination with calcium phosphates.
Bolander, Johanna; Chai, Yoke Chin; Geris, Liesbet et al.
2016In Biomaterials, 86, p. 106-18
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Keywords :
Bone tissue engineering; Calcium phosphate; Cell signalling; Modelling; Osteogenesis; Progenitor cell
Abstract :
[en] The development of osteoinductive calcium phosphate- (CaP) based biomaterials has, and continues to be, a major focus in the field of bone tissue engineering. However, limited insight into the spatiotemporal activation of signalling pathways has hampered the optimisation of in vivo bone formation and subsequent clinical translation. To gain further knowledge regarding the early molecular events governing bone tissue formation, we combined human periosteum derived progenitor cells with three types of clinically used CaP-scaffolds, to obtain constructs with a distinct range of bone forming capacity in vivo. Protein phosphorylation together with gene expression for key ligands and target genes were investigated 24 hours after cell seeding in vitro, and 3 and 12 days post ectopic implantation in nude mice. A computational modelling approach was used to deduce critical factors for bone formation 8 weeks post implantation. The combined Ca(2+)-mediated activation of BMP-, Wnt- and PKC signalling pathways 3 days post implantation were able to discriminate the bone forming from the non-bone forming constructs. Subsequently, a mathematical model able to predict in vivo bone formation with 96% accuracy was developed. This study illustrates the importance of defining and understanding CaP-activated signalling pathways that are required and sufficient for in vivo bone formation. Furthermore, we demonstrate the reliability of mathematical modelling as a tool to analyse and deduce key factors within an empirical data set and highlight its relevance to the translation of regenerative medicine strategies.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
Bolander, Johanna
Chai, Yoke Chin
Geris, Liesbet  ;  Université de Liège > Département d'aérospatiale et mécanique > Génie biomécanique
Schrooten, Jan
Lambrechts, Dennis
Roberts, Scott J.
Luyten, Frank P.
Language :
English
Title :
Early BMP, Wnt and Ca(2+)/PKC pathway activation predicts the bone forming capacity of periosteal cells in combination with calcium phosphates.
Publication date :
2016
Journal title :
Biomaterials
ISSN :
0142-9612
eISSN :
1878-5905
Publisher :
Elsevier, United Kingdom
Volume :
86
Pages :
106-18
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]
Commentary :
Copyright (c) 2016 Elsevier Ltd. All rights reserved.
Available on ORBi :
since 17 July 2016

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