Department of Endodontics, Asahi University School of Dentistry, Gifu, Japan.
Department of Oral Biochemistry, Asahi University School of Dentistry, Gifu, Japan.
Connect Tissue Res. 2021 Nov;62(6):689-697. doi: 10.1080/03008207.2020.1865937. Epub 2021 Jan 12.
: In our previous study, we demonstrated that hyaluronan induces odontoblastic differentiation of dental pulp stem cells via interactions with CD44. However, it remains unclear whether CD44 expression by dental pulp stem cells is required for odontoblastic differentiation.: We searched for a compound other than hyaluronan that induces odontoblastic differentiation of dental pulp stem cells and used western blotting to determine whether CD44 is involved in the induction of odontoblastic differentiation by the compound. We further validated the cell signaling details of the compound-induced expression of dentin sialophosphoprotein (DSPP), which is known as a marker of odontoblastic differentiation.: We investigated shikonin, which is one of the derivatives of naphthoquinone, the skeleton of vitamin K. Shikonin-induced expression of DSPP was inhibited by PI3K, AKT, and mTOR inhibitors. Additionally, shikonin-induced expression of DSPP was inhibited in dental pulp stem cells transfected with siRNA against CD44.: Shikonin can stimulate dental pulp stem cells to undergo odontoblastic differentiation through a mechanism involving the AKT-mTOR signaling pathway and CD44. Although expression of CD44 is important for inducing odontoblastic differentiation of dental pulp stem cells, the relationship between the AKT-mTOR signaling pathway and CD44 expression, in the context of shikonin stimulation, has not yet been elucidated. This study suggests that shikonin may be useful for inducing odontoblastic differentiation of dental pulp stem cells, and that it may have clinical applications, including protection of the dental pulp.
在我们之前的研究中，我们证明透明质酸通过与 CD44 的相互作用诱导牙髓干细胞的成牙本质分化。然而，牙髓干细胞的 CD44 表达是否是牙本质分化所必需的，目前尚不清楚。我们寻找了一种除透明质酸以外的化合物，该化合物能诱导牙髓干细胞的牙本质分化，并通过 Western blot 确定 CD44 是否参与该化合物诱导的牙本质分化。我们进一步验证了该化合物诱导牙本质涎磷蛋白（DSPP）表达的细胞信号细节，DSPP 是牙本质分化的标志物之一。我们研究了萘醌的衍生物之一紫草素，它是维生素 K 的骨架。PI3K、AKT 和 mTOR 抑制剂抑制了紫草素诱导的 DSPP 表达。此外，用针对 CD44 的 siRNA 转染的牙髓干细胞中，紫草素诱导的 DSPP 表达受到抑制。紫草素可以通过 AKT-mTOR 信号通路和 CD44 来刺激牙髓干细胞向成牙本质细胞分化。尽管 CD44 的表达对于诱导牙髓干细胞的牙本质分化很重要，但在紫草素刺激的情况下，AKT-mTOR 信号通路和 CD44 表达之间的关系尚未阐明。本研究表明，紫草素可能有助于诱导牙髓干细胞的牙本质分化，并且可能具有临床应用，包括牙髓保护。
