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dc.contributor.authorPrendergast, Patricken
dc.contributor.authorMurphy, Paulaen
dc.contributor.editorBoris Kablaren
dc.date.accessioned2011-03-11T13:51:12Z
dc.date.available2011-03-11T13:51:12Z
dc.date.issued2011en
dc.date.submitted2011en
dc.identifier.citationRoddy KA, Prendergast PJ, Murphy P, Mechanical Influences on Morphogenesis of the Knee Joint Revealed through Morphological, Molecular and Computational Analysis of Immobilised Embryos., PloS one, 6, 2, 2011, e17526en
dc.identifier.issn1932-6203en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/53205
dc.descriptionPUBLISHEDen
dc.description.abstractVery little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint.en
dc.description.sponsorshipThis work was supported by a TCD Overhead Investment Plan (OIP) Interdiscipinary Award, Wellcome Trust project grant (083539/Z/07/Z) and Science Foundation Ireland (Programme Award 02/IN1/B267). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.format.extente17526en
dc.language.isoenen
dc.publisherUniversity of Edinburgh (datashare)en
dc.relation.ispartofseriesYen
dc.relation.ispartofseriesPloS oneen
dc.relation.ispartofseries6en
dc.relation.ispartofseries2en
dc.rightsYen
dc.subjectBioengineeringen
dc.subjectGeneticsen
dc.subjectsynovial jointsen
dc.titleMechanical Influences on Morphogenesis of the Knee Joint Revealed through Morphological, Molecular and Computational Analysis of Immobilised Embryos.en
dc.title.alternativeRoles of Skeletal Muscle in Organ Developmenten
dc.typeJournal Articleen
dc.contributor.sponsorWellcome Trusten
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/pprenderen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/pmurphy3en
dc.identifier.rssinternalid71654en
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0017526en
dc.contributor.sponsorGrantNumber083539/Z/07/Zen
dc.contributor.sponsorGrantNumber02/IN1/B267en
dc.subject.TCDThemeGenes & Societyen
dc.subject.TCDThemeNext Generation Medical Devicesen
dc.identifier.rssurihttp://dx.doi.org/10.1371/journal.pone.0017526en
dc.status.accessibleNen


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