Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Beijing Stomatology Hospital, Capital Medical University, Beijing, China.
Department of General Dentistry, School of Stomatology, Beijing Stomatology Hospital, Capital Medical University, Beijing, China.
J Cell Physiol. 2020 Nov;235(11):8432-8445. doi: 10.1002/jcp.29687. Epub 2020 Apr 4.
Enhancing the functions of mesenchymal stem cells (MSCs) is considered a potential approach for promoting tissue regeneration. In the present study, we investigate the role of HOXC8 in regulating differentiation and migration by using stem cells of the apical papilla (SCAPs). Our results showed that overexpression of HOXC8 suppressed the osteo-/dentinogenic differentiation, as detected by measuring alkaline phosphatase activity, in vitro mineralization, and the expressions of dentin sialophosphoprotein, dentin matrix acidic phosphoprotein 1, bone sialoprotein, runt-related transcription factor 2, and osterix in SCAPs, and inhibited in vivo osteo-/dentinogenesis of SCAPs. In addition, knockdown of HOXC8 promoted the osteo-/dentinogenic differentiation potentials of SCAPs. Mechanically, HOXC8 enhanced KDM1A transcription by directly binding to its promoter. HOXC8 and KDM1A also inhibited the migration and chemotaxis abilities of SCAPs. To sum up, HOXC8 negatively regulated the osteo-/dentinogenic differentiation and migration abilities of SCAPs by directly enhancing KDM1A transcription and indicated that HOXC8 and KDM1A could serve as potential targets for enhancing dental MSC mediated tissue regeneration.
增强间充质干细胞（MSCs）的功能被认为是促进组织再生的一种潜在方法。在本研究中，我们使用根尖乳头干细胞（SCAPs）研究 HOXC8 在调节分化和迁移中的作用。我们的结果表明，HOXC8 的过表达通过测量碱性磷酸酶活性、体外矿化以及牙本质涎磷蛋白、牙本质基质酸性磷酸蛋白 1、骨唾液蛋白、 runt 相关转录因子 2 和成骨蛋白的表达来抑制 SCAPs 的成骨/成牙本质分化，并抑制 SCAPs 的体内成骨/成牙本质发生。此外，下调 HOXC8 促进了 SCAPs 的成骨/成牙本质分化潜能。在机制上，HOXC8 通过直接结合其启动子增强 KDM1A 的转录。HOXC8 和 KDM1A 还抑制了 SCAPs 的迁移和趋化能力。总之，HOXC8 通过直接增强 KDM1A 的转录来负调控 SCAPs 的成骨/成牙本质分化和迁移能力，并表明 HOXC8 和 KDM1A 可以作为增强牙齿 MSC 介导的组织再生的潜在靶点。
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