关键词: Network pharmacology Osteogenesis PI3K/Akt pathway Phenytoin Small molecule drugs

来  源:   DOI:10.1016/j.reth.2023.06.015   PDF(Pubmed)

Abstract:
UNASSIGNED: We mainly studied the mechanism by which phenytoin promotes osteogenic differentiation of human jawbone marrow stem cells.
UNASSIGNED: Bone marrow stem cells were extracted from jaw bone tissue debris obtained from 5 subjects undergoing implant restoration. Osteogenic and adipogenic experiments proved cells stemness, and the expression of ALP, RUNX2, and OSX were detected by qPCR and Western blot. High-throughput sequencing was used to extract differentially expressed genes, the network database predicted phenytoin drug targets, GO and KEGG enrichment combined with PPI network diagram to analyze the osteogenesis mechanism.
UNASSIGNED: Calcium nodules and lipid droplet formation were observed in osteogenic and adipogenic experiments. The concentration of phenytoin within 100 mg/L does not produce cytotoxicity. The results of PCR and WB indicated that 50 mg/L phenytoin significantly promoted the expression of ALP and RUNX2, and 25 mg/L phenytoin significantly promoted the expression of OSX. The results of network pharmacology suggest that phenytoin promotes bone formation by up-regulating FGFR2, S1PR1, TGFB3, VCAN core proteins and activating PI3K/Akt pathway.
UNASSIGNED: Phenytoin activated the PI3K/Akt pathway to regulate the osteogenic differentiation of human jawbone marrow stem cells. https://data.mendeley.com/datasets/t3xstktt93/1.
摘要:
我们主要研究了苯妥英促进人颌骨骨髓干细胞成骨分化的机制。
从5名接受植入物修复的受试者获得的颌骨组织碎片中提取骨髓干细胞。成骨和成脂实验证明了细胞的干性,以及ALP的表达,通过qPCR和Western印迹检测RUNX2和OSX。高通量测序用于提取差异表达基因,网络数据库预测苯妥英钠药物靶点,GO和KEGG富集结合PPI网络图分析成骨机制。
在成骨和成脂实验中观察到钙结节和脂滴形成。苯妥英的浓度在100mg/L以内不产生细胞毒性。PCR和WB结果表明,50mg/L苯妥英显著促进ALP和RUNX2的表达,25mg/L苯妥英显著促进OSX的表达。网络药理学结果表明,苯妥英通过上调FGFR2、S1PR1、TGFB3、VCAN核心蛋白和激活PI3K/Akt通路促进骨形成。
苯妥英激活PI3K/Akt通路调节人颌骨骨髓干细胞成骨分化。https://data.mendeley.com/datasets/t3xstktt93/1.
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