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bioRxiv · 10.1101/2020.02.07.938811

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

Hodgkinson, T.·Tsimbouri, M.·Llopis-Hernandez, V.·Campsie, P.·Scurr, D.·Childs, P.·Phillips, D.·Donnelly, S.·Wells, J.·Salmeron-Sanchez, M.·Burgess, K.·Alexander, M. R.·Vassalli, M.·Oreffo, R.·Reid, S. R.·France, D.·Dalby, M. J.
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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 the osteogenic differentiation of MSCs, in the absence of off-target differentiation. We show that this differentiation method, which does not rely on the addition of exogenous growth factors to the culture media, provides an artefact-free approach to identifying bioactive metabolites that specifically and potently induce osteogenesis. We first identify a highly specific metabolite as the endogenous steroid, cholesterol sulphate. Next, a screen of other small molecules with a similar steroid scaffold identified fludrocortisone acetate as being both specific and having highly potent osteogenic-inducing activity. These findings demonstrate that physical priciples can be used to identify bioactive metabolites and then metabolite potency can be optimised by examining structure-function relationship.

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Hodgkinson, T., Tsimbouri, M., Llopis-Hernandez, V., Campsie, P., Scurr, D., Childs, P., Phillips, D., Donnelly, S., Wells, J., Salmeron-Sanchez, M., Burgess, K., Alexander, M. R., Vassalli, M., Oreffo, R., Reid, S. R., France, D., Dalby, M. J.. 2020-02-07. The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells. https://doi.org/10.1101/2020.02.07.938811

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