首页> 外文期刊>The Journal of toxicological sciences >Phenytoin stimulates chondrogenic differentiation in mouse clonal chondrogenic ec cells, atdc5.
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Phenytoin stimulates chondrogenic differentiation in mouse clonal chondrogenic ec cells, atdc5.

机译:苯妥英钠刺激小鼠克隆软骨生成ec细胞atdc5中的软骨生成分化。

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Phenytoin (DPH) is known to affect bone formation. However, the mechanism of this effect has not been well understood. In this study, we evaluated the effects of DPH on cartilage formation in a model system using ATDC5 cells, a clonal murine chondrogenic cell line. Alcian blue staining for cartilage nodules and real-time reverse-transcription polymerase chain reaction for the expression of genes encoding type II collagen, aggrecan, transforming growth factor (TGF)-beta1, bone morphogenetic protein (BMP)-4, parathyroid hormone-related peptide (PTHrP), indian hedgehog (Ihh), and patched (Ptc) were performed in ATDC5 cells cultured with DPH. The ATDC5 cells demonstrated enhanced cartilage formation in cultures with DPH. During promoted chondrogenic differentiation, it was observed that DPH increased the mRNA expression of TGF-beta1, BMP-4, Ihh, and Ptc, in a dose-dependent manner on Days 5 to 15. In contrast, other antiepileptic drugs, phenobarbital and valproic acid had no effects on chondrogenesis in ATDC5 cells and osteogenesis in MC3T3-E1 cells. Our results provide fundamental evidence that DPH has a direct stimulatory effect on cartilage formation by regulating TGF-beta and hedgehog signaling molecules, and that DPH effect on bone formation, including chondrogenesis and osteogenesis, is distinct from other antiepileptic drugs as suggested in clinical settings.
机译:苯妥英(DPH)会影响骨骼形成。但是,这种作用的机理还没有被很好地理解。在这项研究中,我们评估了ATPH5细胞(一种克隆的小鼠软骨细胞系)在模型系统中DPH对软骨形成的影响。软骨结节的阿尔辛蓝染色和实时逆转录聚合酶链反应,用于表达编码II型胶原蛋白,聚集蛋白聚糖,转化生长因子(TGF)-beta1,骨形态发生蛋白(BMP)-4,甲状旁腺激素相关的基因肽(PTHrP),印度刺猬(Ihh)和贴片(Ptc)在用DPH培养的ATDC5细胞中进行。 ATDC5细胞在DPH培养物中显示出增强的软骨形成。在促进软骨形成的分化过程中,观察到DPH在第5到15天以剂量依赖的方式增加了TGF-beta1,BMP-4,Ihh和Ptc的mRNA表达。相比之下,其他抗癫痫药苯巴比妥和丙戊酸酸对ATDC5细胞的软骨形成和MC3T3-E1细胞的成骨没有影响。我们的研究结果提供了基本证据,表明DPH通过调节TGF-β和刺猬信号分子对软骨形成具有直接的刺激作用,并且DPH对骨形成的影响(包括软骨形成和成骨作用)与其他抗癫痫药物在临床环境中不同。

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