Biggs, M.J.P., Richards, R.G., Gadegaard, N. , Wilkinson, C.D.W., Oreffo, R.O.C. and Dalby, M.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), pp. 5094-5103. (doi: 10.1016/j.biomaterials.2009.05.049)
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Abstract
The physiochemical characteristics of a material with <i>in vivo</i> 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 <i>in vitro</i> 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 µm 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 µm 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
| Item Type: | Articles |
|---|---|
| Keywords: | Osteoblasts, mesenchymal stem cells, focal adhesions, nanotopography, ERK/MAPK |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Wilkinson, Professor Christopher and Gadegaard, Professor Nikolaj and Dalby, Professor Matthew |
| Authors: | Biggs, M.J.P., Richards, R.G., Gadegaard, N., Wilkinson, C.D.W., Oreffo, R.O.C., and Dalby, M.J. |
| Subjects: | Q Science > QR Microbiology > QR180 Immunology Q Science > QR Microbiology |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Science and Engineering > School of Engineering College of Science and Engineering > School of Engineering > Biomedical Engineering |
| Journal Name: | Biomaterials |
| ISSN: | 0142-9612 |
| ISSN (Online): | 1878-5905 |
| Published Online: | 21 June 2009 |
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