Phenytoin regulates osteogenic differentiation of human bone marrow stem cells by PI3K/Akt pathway

苯妥英通过PI3K/Akt通路调控人骨髓干细胞成骨分化

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作者:Zeliang Zhang, Wei Shang, Xicong Zhao, Lisong Lin

Background

We mainly studied the mechanism by which phenytoin promotes osteogenic differentiation of human jawbone marrow stem cells.

Conclusions

Phenytoin activated the PI3K/Akt pathway to regulate the osteogenic differentiation of human jawbone marrow stem cells. https://data.mendeley.com/datasets/t3xstktt93/1.

Methods

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.

Results

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. Conclusions: Phenytoin activated the PI3K/Akt pathway to regulate the osteogenic differentiation of human jawbone marrow stem cells. https://data.mendeley.com/datasets/t3xstktt93/1.

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