Orthodontic Section, Department of Preventive Dentistry, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Henry-Dunant Rd, Pathumwan, Bangkok 10330, Thailand.
Cell Biol Int. 2019 May;43(5):506-515. doi: 10.1002/cbin.11116. Epub 2019 Mar 12.
Mechanical stimuli have been shown to play an important role in directing stem cell fate and maintenance of tissue homeostasis. One of the functions of the mechanoresponsive tissue periodontal ligament (PDL) is to withstand the functional forces within the oral cavity. Periodontal ligament stem cells (PDLSCs) derived from periodontal tissue have been demonstrated to be able to respond directly to mechanical forces. However, the mechanisms of action of mechanical force on PDLSCs are not totally understood. The aim of this study was to investigate the mechanisms by which compressive force affects PDLSCs, especially their stemness properties. PDLSCs were established from extracted human third molars; their stem cell characteristics were validated by detecting the expression of stem cell markers and confirming their ability to differentiate into osteogenic and adipogenic lineages. PDLSCs were subjected to various magnitudes of static compressive force (0 [control], 0.5, 1.0, 1.5, or 2 g/cm ). Application of 1.0 g/cm compressive force significantly upregulated a panel of stem cell marker genes, including NANOG and OCT4. Conversely, higher force magnitudes downregulated these genes. Mechanical loading also upregulated periostin, a matrix protein that plays important roles in tissue morphogenesis. Interestingly, knockdown of periostin using siRNA abolished force-induced stem cell marker expression in PDLSCs. This study suggests a proper magnitude of compressive force could be one important factor involved in the modulation of the pluripotency of PDLSCs through the action of periostin. The precise mechanism by which periostin regulates stemness requires further detailed investigation.
机械刺激在指导干细胞命运和维持组织内稳态方面发挥着重要作用。对机械刺激有响应的组织之一是牙周韧带（PDL），其功能是承受口腔内的功能性力量。已经证明来源于牙周组织的牙周韧带干细胞（PDLSCs）能够直接对机械力作出响应。然而，机械力对 PDLSCs 的作用机制尚未完全阐明。本研究旨在探讨压力对 PDLSCs 的作用机制，尤其是对其干细胞特性的影响。从提取的人第三磨牙中建立 PDLSCs；通过检测干细胞标志物的表达并证实其向成骨和成脂谱系分化的能力来验证其干细胞特性。将 PDLSCs 施加不同大小的静态压缩力（0 [对照]、0.5、1.0、1.5 或 2 g/cm）。施加 1.0 g/cm 的压缩力可显著上调一组干细胞标志物基因，包括 NANOG 和 OCT4。相反，更高的力大小则下调这些基因。机械加载还上调了外骨蛋白，一种在组织形态发生中起重要作用的基质蛋白。有趣的是，使用 siRNA 敲低外骨蛋白可消除 PDLSCs 中力诱导的干细胞标志物表达。本研究表明，适当的压缩力大小可能是通过外骨蛋白作用调节 PDLSCs 多能性的一个重要因素。外骨蛋白调节干细胞特性的确切机制需要进一步详细研究。
