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

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.