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

Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces: the role of focal adhesion maturation.
Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces: the role of focal adhesion maturation.
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 orthopedic devices. In this study, the FDA-approved plastic polycaprolactone was embossed with nanometric grooves and the response of primary and immortalized osteoprogenitor cells observed. Nanometric groove dimensions were 240 nm or 540 nm deep and 12.5 ?m 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 lower proportions of mature adhesions relative to planar controls. Down-regulation of the osteoblast marker genes RUNX2 and BMPR2 in primary and immortalized 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.
bone formation, contact guidance, focal adhesion, tissue engineering, topography
1742-7061
651-660
Cassidy, John W.
4993469e-69bb-42da-85da-be4acedc42ee
Roberts, Jemma N.
dab50844-4015-4a42-9876-932c8a94c875
Smith, Carol-Anne
396c04b3-8e95-463a-abf4-cd1e0e98611a
Robertson, Mary
4c243424-d31b-4450-a45c-4aca5b7c2834
White, Kate
ad592ed1-c133-4e3a-abed-3803a6d5531c
Biggs, Manus J.
90caf50f-5da2-437b-a957-d9cc57bebb14
Oreffo, Richard O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Dalby, Matthew J.
25dcae6a-8289-4169-abb7-c45fff0bafdc
Cassidy, John W.
4993469e-69bb-42da-85da-be4acedc42ee
Roberts, Jemma N.
dab50844-4015-4a42-9876-932c8a94c875
Smith, Carol-Anne
396c04b3-8e95-463a-abf4-cd1e0e98611a
Robertson, Mary
4c243424-d31b-4450-a45c-4aca5b7c2834
White, Kate
ad592ed1-c133-4e3a-abed-3803a6d5531c
Biggs, Manus J.
90caf50f-5da2-437b-a957-d9cc57bebb14
Oreffo, Richard O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Dalby, Matthew J.
25dcae6a-8289-4169-abb7-c45fff0bafdc

Cassidy, John W., Roberts, Jemma N., Smith, Carol-Anne, Robertson, Mary, White, Kate, Biggs, Manus J., Oreffo, Richard O.C. and Dalby, Matthew J. (2014) Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces: the role of focal adhesion maturation. Acta Biomaterialia, 10 (2), 651-660. (PMID:24252447)

Record type: Article

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 orthopedic devices. In this study, the FDA-approved plastic polycaprolactone was embossed with nanometric grooves and the response of primary and immortalized osteoprogenitor cells observed. Nanometric groove dimensions were 240 nm or 540 nm deep and 12.5 ?m 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 lower proportions of mature adhesions relative to planar controls. Down-regulation of the osteoblast marker genes RUNX2 and BMPR2 in primary and immortalized 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.

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Published date: February 2014
Keywords: bone formation, contact guidance, focal adhesion, tissue engineering, topography
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 367171
URI: https://eprints.soton.ac.uk/id/eprint/367171
ISSN: 1742-7061
PURE UUID: 5132fb6d-14e3-431e-a8b2-3e0d42b651a7
ORCID for Richard O.C. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

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Date deposited: 23 Jul 2014 17:23
Last modified: 06 Jun 2018 12:53

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