title: Synergistic activity of polarised osteoblasts inside condensations cause their differentiation.
abstract: Condensation of pre-osteogenic, or pre-chondrogenic, cells is the first of a series of processes that initiate skeletal development. We present a validated, novel, three-dimensional agent-based model of in vitro intramembranous osteogenic condensation. The model, informed by system heterogeneity and relying on an interaction-reliant strategy, is shown to be sensitive to 'rules' capturing condensation growth and can be employed to track activity of individual cells to observe their macroscopic impact. It, therefore, makes available previously inaccessible data, offering new insights and providing a new context for exploring the emergence, as well as normal and abnormal development, of osteogenic structures. Of the several stages of condensation we investigate osteoblast 'burial' within the osteoid they deposit. The mechanisms underlying entrapment--required for osteoblasts to differentiate into osteocytes--remain a matter of conjecture with several hypotheses claiming to capture this important transition. Computational examination of this transition indicates that osteoblasts neither turn off nor slow down their matrix secreting genes--a widely held view; nor do they secrete matrix randomly. The model further reveals that osteoblasts display polarised behaviour to deposit osteoid. This is both an important addition to our understanding of condensation and an important validation of the model's utility.
authors.affiliation: 1] Department of Engineering Science, University of Oxford, Oxford, OX1 3PJ, UK [2] Department of Computer Science, University of Sheffield, Sheffield, S1 4DP, UK.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Kaul
authors.affiliation: Department of Biology, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Hall
authors.affiliation: Department of Infection, Immunity, and Inflammation, University of Leicester, Leicester, LE1 9HN, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Newby
authors.affiliation: Department of Mechanical Engineering, University College London, London, WC1E 7JE, UK.
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Ventikos
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D016764:Cell Polarity; D049109:Cell Proliferation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis