The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells

Hodgkinson, T. et al. (2021) The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells. Science Advances, 7(9), eabb7921. (doi: 10.1126/sciadv.abb7921) (PMID:33637520)

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Abstract

Bioactive metabolites have wide-ranging biological activities and are a potential source of future research and therapeutic tools. Here, we use nanovibrational stimulation to induce osteogenic differentiation of mesenchymal stem cells, in the absence of off-target, nonosteogenic differentiation. We show that this differentiation method, which does not rely on the addition of exogenous growth factors to culture media, provides an artifact-free approach to identifying bioactive metabolites that specifically and potently induce osteogenesis. We first identify a highly specific metabolite, cholesterol sulfate, an endogenous steroid. Next, a screen of other small molecules with a similar steroid scaffold identified fludrocortisone acetate with both specific and highly potent osteogenic-inducing activity. Further, we implicate cytoskeletal contractility as a measure of osteogenic potency and cell stiffness as a measure of specificity. These findings demonstrate that physical principles can be used to identify bioactive metabolites and then enable optimization of metabolite potency can be optimized by examining structure-function relationships.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Burgess, Dr Karl and Salmeron-Sanchez, Professor Manuel and Hodgkinson, Dr Tom and Childs, Dr Peter and Dalby, Professor Matthew and Tsimbouri, Dr Monica and Llopis-Hernandez, Dr Virginia and France, Dr David and Phillips, Mr David and Vassalli, Dr Massimo and Donnelly, Sam
Authors: Hodgkinson, T., Tsimbouri, P. M., Llopis-Hernandez, V., Campsie, P., Scurr, D., Childs, P. G., Phillips, D., Donnelly, S., Wells, J. A., O’Brien, F. J., Salmeron-Sanchez, M., Burgess, K., Alexander, M., Vassalli, M., Oreffo, R. O.C., Reid, S., France, D. J., and Dalby, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Science and Engineering > School of Chemistry
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Science Advances
Publisher:American Association for the Advancement of Science
ISSN:2375-2548
ISSN (Online):2375-2548
Published Online:26 February 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Science Advances 7(9):eabb7921
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173494Rapid Bone Graft Synthesis Through Dual Piezoelectric/Nanomechaniocal StimulationMatthew DalbyBiotechnology and Biological Sciences Research Council (BBSRC)BB/P00220X/1Institute of Molecular, Cell & Systems Biology
173192Engineering growth factor microenvironments- a new therapeutic paradigm for regenerative medicineManuel Salmeron-SanchezEngineering and Physical Sciences Research Council (EPSRC)EP/P001114/1ENG - Biomedical Engineering
172525Developing the NanoKick bioreactor to enable tissue engineered bone graft and use of metabolomics to identify bone specific drug candidatesMatthew DalbyEngineering and Physical Sciences Research Council (EPSRC)EP/N013905/1Institute of Molecular, Cell & Systems Biology