Recent advances on small molecules in osteogenic differentiation of stem cells and the underlying signaling pathways.
Recent advances on small molecules in osteogenic differentiation of stem cells and the underlying signaling pathways.
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DOI：
10.1186/s13287-022-03204-4
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发表时间：
2022-11-12
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
作者：
骨相关疾病是老年人发病率和死亡率的主要原因，目前的治疗方法导致愈合不足和几种并发症。使用干细胞的再生医学是治疗骨折和骨骼缺陷的一个很有前途的研究领域。使用使细胞发育向首选谱系转变的试剂来分化干细胞需要激活某些细胞内信号通路，其中许多已知在胚胎学阶段诱导成骨。通过激活这些信号通路来模拟胚胎成骨一直是许多成骨研究的重点。成骨信号的激活可以通过使用小分子来完成。其中一些药物，如他汀类、二甲双胍、腺苷和地塞米松，也有其他临床用途，但也显示出成骨能力。另一方面，其他一些分子，如T63和四氢喹啉类化合物，在临床上也没有得到很好的认识。成骨小分子通过激活已知的与成骨相关的信号通路发挥作用。这些信号通路包括BMP/Smad、Wnt、Hedgehog等较为知名的信号通路，以及雌激素信号和神经肽信号等辅助信号通路。本文综述了小分子介导的成骨分化的最新数据，这些分子可能的辅助剂，以及每个小分子发挥作用的信号通路。
Bone-related diseases are major contributors to morbidity and mortality in elderly people and the current treatments result in insufficient healing and several complications. One of the promising areas of research for healing bone fractures and skeletal defects is regenerative medicine using stem cells. Differentiating stem cells using agents that shift cell development towards the preferred lineage requires activation of certain intracellular signaling pathways, many of which are known to induce osteogenesis during embryological stages. Imitating embryological bone formation through activation of these signaling pathways has been the focus of many osteogenic studies. Activation of osteogenic signaling can be done by using small molecules. Several of these agents, e.g., statins, metformin, adenosine, and dexamethasone have other clinical uses but have also shown osteogenic capacities. On the other hand, some other molecules such as T63 and tetrahydroquinolines are not as well recognized in the clinic. Osteogenic small molecules exert their effects through the activation of signaling pathways known to be related to osteogenesis. These pathways include more well-known pathways including BMP/Smad, Wnt, and Hedgehog as well as ancillary pathways including estrogen signaling and neuropeptide signaling. In this paper, we review the recent data on small molecule-mediated osteogenic differentiation, possible adjunctive agents with these molecules, and the signaling pathways through which each small molecule exerts its effects.
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影响因子：
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作者：
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