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The use of nanoscale topography to modulate the dynamics of adhesion formation in primary osteoblasts and ERK/MAPK signalling in STRO-1+enriched skeletal stem cells

The use of nanoscale topography to modulate the dynamics of adhesion formation in primary osteoblasts and ERK/MAPK signalling in STRO-1+enriched skeletal stem cells
The use of nanoscale topography to modulate the dynamics of adhesion formation in primary osteoblasts and ERK/MAPK signalling in STRO-1+enriched skeletal stem cells
The physiochemical characteristics of a material with in vivo applications are critical for the clinical success of the implant and regulate both cellular adhesion and differentiated cellular function. Topographical modification of an orthopaedic implant may be a viable method to guide tissue integration and has been shown in vitro to dramatically influence osteogenesis, inhibit bone resorption and regulate integrin mediated cell adhesion. Integrins function as force dependant mechanotransducers, acting via the actin cytoskeleton to translate tension applied at the tissue level to changes in cellular function via intricate signalling pathways. In particular the ERK/MAPK signalling cascade is a known regulator of osteospecific differentiation and function. Here we investigate the effects of nanoscale pits and grooves on focal adhesion formation in human osteoblasts (HOBs) and the ERK/MAPK signalling pathway in mesenchymal populations. Nanopit arrays disrupted adhesion formation and cellular spreading in HOBs and impaired osteospecific differentiation in skeletal stem cells. HOBs cultured on 10 ?m wide groove/ridge arrays formed significantly less focal adhesions than cells cultured on planar substrates and displayed negligible differentiation along the osteospecific lineage, undergoing up-regulations in the expression of adipospecific genes. Conversely, osteospecific function was correlated to increased integrin mediated adhesion formation and cellular spreading as noted in HOBS cultured on 100 ?m wide groove arrays. Here osteospecific differentiation and function was linked to focal adhesion growth and FAK mediated activation of the ERK/MAPK signalling pathway in mesenchymal populations.

osteoblasts, mesenchymal stem cells, focal adhesions, nanotopography, erk/mapk
0142-9612
5094-5103
Biggs, Manus J.
90caf50f-5da2-437b-a957-d9cc57bebb14
Richards, R. Geoff
69d42d1f-d1dd-4f1b-8766-03df55a5f2ca
Gadegaard, Nikolaj
bf72c3d1-e6a7-48b4-a968-c496b655bd98
Wilkinson, Chris D.W.
ea556659-2ba1-43a8-b8d3-37e4bfaffd41
Oreffo, Richard O.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Dalby, Matthew J.
25dcae6a-8289-4169-abb7-c45fff0bafdc
Biggs, Manus J.
90caf50f-5da2-437b-a957-d9cc57bebb14
Richards, R. Geoff
69d42d1f-d1dd-4f1b-8766-03df55a5f2ca
Gadegaard, Nikolaj
bf72c3d1-e6a7-48b4-a968-c496b655bd98
Wilkinson, Chris D.W.
ea556659-2ba1-43a8-b8d3-37e4bfaffd41
Oreffo, Richard O.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Dalby, Matthew J.
25dcae6a-8289-4169-abb7-c45fff0bafdc

Biggs, Manus J., Richards, R. Geoff, Gadegaard, Nikolaj, Wilkinson, Chris D.W., Oreffo, Richard O. and Dalby, Matthew J. (2009) The use of nanoscale topography to modulate the dynamics of adhesion formation in primary osteoblasts and ERK/MAPK signalling in STRO-1+enriched skeletal stem cells. Biomaterials, 30 (28), 5094-5103. (doi:10.1016/j.biomaterials.2009.05.049). (PMID:19539986)

Record type: Article

Abstract

The physiochemical characteristics of a material with in vivo applications are critical for the clinical success of the implant and regulate both cellular adhesion and differentiated cellular function. Topographical modification of an orthopaedic implant may be a viable method to guide tissue integration and has been shown in vitro to dramatically influence osteogenesis, inhibit bone resorption and regulate integrin mediated cell adhesion. Integrins function as force dependant mechanotransducers, acting via the actin cytoskeleton to translate tension applied at the tissue level to changes in cellular function via intricate signalling pathways. In particular the ERK/MAPK signalling cascade is a known regulator of osteospecific differentiation and function. Here we investigate the effects of nanoscale pits and grooves on focal adhesion formation in human osteoblasts (HOBs) and the ERK/MAPK signalling pathway in mesenchymal populations. Nanopit arrays disrupted adhesion formation and cellular spreading in HOBs and impaired osteospecific differentiation in skeletal stem cells. HOBs cultured on 10 ?m wide groove/ridge arrays formed significantly less focal adhesions than cells cultured on planar substrates and displayed negligible differentiation along the osteospecific lineage, undergoing up-regulations in the expression of adipospecific genes. Conversely, osteospecific function was correlated to increased integrin mediated adhesion formation and cellular spreading as noted in HOBS cultured on 100 ?m wide groove arrays. Here osteospecific differentiation and function was linked to focal adhesion growth and FAK mediated activation of the ERK/MAPK signalling pathway in mesenchymal populations.

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More information

Published date: October 2009
Keywords: osteoblasts, mesenchymal stem cells, focal adhesions, nanotopography, erk/mapk

Identifiers

Local EPrints ID: 181677
URI: https://eprints.soton.ac.uk/id/eprint/181677
ISSN: 0142-9612
PURE UUID: e8bb8d2a-6d57-4ffc-a926-22c431741e7a
ORCID for Richard O. Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

Catalogue record

Date deposited: 18 Apr 2011 09:14
Last modified: 19 Nov 2019 01:52

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