The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells.
The use of nanovibration to discover specific and potent bioactive metabolites that stimulate osteogenic differentiation in mesenchymal stem cells.
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利用纳米振动发现刺激间充质干细胞成骨分化的特异性和有效的生物活性代谢物。
DOI：
10.1126/sciadv.abb7921
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发表时间：
2021-03
期刊：
影响因子：
13.6
通讯作者：
Dalby MJ
中科院分区：
文献类型：
--
作者：
Hodgkinson T;Tsimbouri PM;Llopis-Hernandez V;Campsie P;Scurr D;Childs PG;Phillips D;Donnelly S;Wells JA;O'Brien FJ;Salmeron-Sanchez M;Burgess K;Alexander M;Vassalli M;Oreffo ROC;Reid S;France DJ;Dalby MJ
成骨活性代谢物可以在纳米振动培养中鉴定，并且具有增强的特异性和效力。生物活性代谢物具有广泛的生物活性，是未来研究和治疗工具的潜在来源。在这里，我们使用纳米振动刺激诱导间充质干细胞的成骨分化，在没有脱靶，非成骨分化。我们表明，这种分化方法，它不依赖于添加外源性生长因子的培养基，提供了一种无伪影的方法来识别生物活性代谢产物，特异性和有效地诱导成骨。我们首先确定一个高度特异性的代谢产物，胆固醇硫酸盐，内源性类固醇。接下来，对具有类似类固醇支架的其他小分子进行筛选，鉴定出具有特异性和高效成骨诱导活性的醋酸氟氢可的松。此外，我们牵连细胞骨架收缩性作为衡量成骨能力和细胞刚度作为衡量特异性。这些发现表明，物理原理可用于鉴定生物活性代谢物，然后通过检查结构-功能关系来优化代谢物效力。
Osteogenic activity metabolites can be identified in nanovibrational culture and have their specificity and potency enhanced. 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.
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影响因子：
120.1
作者：
Cook, David;Brown, Dearg;Pangalos, Menelas N.
通讯作者：
Pangalos, Menelas N.
影响因子：
46.9
作者：
Guijas C;Montenegro-Burke JR;Warth B;Spilker ME;Siuzdak G
通讯作者：
Siuzdak G
影响因子：
4
作者：
Chugh P;Paluch EK
通讯作者：
Paluch EK
DOI：
10.1083/jcb.200610046
发表时间：
2007-02-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ge C;Xiao G;Jiang D;Franceschi RT
通讯作者：
Franceschi RT
影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R