Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces – the role of focal adhesion maturation

Cassidy, J.W., Roberts, J.N. , Smith, C.-A. , Robertson, M., White, K., Biggs, M.J., Oreffo, R.O.C. and Dalby, M.J. (2014) Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces – the role of focal adhesion maturation. Acta Biomaterialia, 10(2), pp. 651-660. (doi:10.1016/j.actbio.2013.11.008) (PMID:24252447) (PMCID:PMC3907683)

Cassidy, J.W., Roberts, J.N. , Smith, C.-A. , Robertson, M., White, K., Biggs, M.J., Oreffo, R.O.C. and Dalby, M.J. (2014) Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces – the role of focal adhesion maturation. Acta Biomaterialia, 10(2), pp. 651-660. (doi:10.1016/j.actbio.2013.11.008) (PMID:24252447) (PMCID:PMC3907683)

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Abstract

The differentiation of progenitor cells is dependent on more than biochemical signalling. Topographical cues in natural bone extracellular matrix guide cellular differentiation through the formation of focal adhesions, contact guidance, cytoskeletal rearrangement and ultimately gene expression. Osteoarthritis and a number of bone disorders present as growing challenges for our society. Hence, there is a need for next generation implantable devices to substitute for, or guide, bone repair in vivo. Cellular responses to nanometric topographical cues need to be better understood in vitro in order to ensure the effective and efficient integration and performance of these orthopaedic devices. In this study, the FDA approved plastic polycaprolactone, was embossed with nanometric grooves and the response of primary and immortalised osteoprogenitor cells observed. Nanometric groove dimensions were 240 nm or 540 nm deep and 12.5 μm wide. Cells cultured on test surfaces followed contact guidance along the length of groove edges, elongated along their major axis and showed nuclear distortion, they formed more focal complexes and a lower proportions of mature adhesions relative to planar controls. Down-regulation of the osteoblast marker genes RUNX2 and BMPR2 in primary and immortalised cells was observed on grooved substrates. Down-regulation appeared to directly correlate with focal adhesion maturation, indicating the involvement of ERK 1/2 negative feedback pathways following integrin mediated FAK activation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robertson, Ms Mary and Roberts, Dr Jemma and Dalby, Professor Matthew and Smith, Mrs Carol-Anne
Authors: Cassidy, J.W., Roberts, J.N., Smith, C.-A., Robertson, M., White, K., Biggs, M.J., Oreffo, R.O.C., and Dalby, M.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Science and Engineering > School of Engineering
Journal Name:Acta Biomaterialia
Publisher:Elsevier
ISSN:1742-7061
ISSN (Online):1878-7568
Copyright Holders:Copyright © 2013 Acta Materialia Inc.
First Published:First published in Acta Biomaterialia 10(2):651-660
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
438161Stem Cell Differentiation & Genomic Processes in Response to Bioactive NanotopographyMatthew DalbyBiotechnology and Biological Sciences Research Council (BBSRC)BB/G008868/1RI MOLECULAR CELL & SYSTEMS BIOLOGY