Dou X W, Park W, Lee S, Zhang Q Z, Carrasco L R, Le A D
1 Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.
2 Department of Advanced General Dentistry, College of Dentistry, Yonsei University, Seoul, South Korea.
J Dent Res. 2017 Mar;96(3):347-354. doi: 10.1177/0022034516680349. Epub 2016 Nov 25.
Mandibular torus (MT) is a common intraoral osseous outgrowth located on the lingual surface of the mandible. Histologic features include hyperplastic bone consisting of mature cortical and trabecular bone. Some theories on the etiology of MT have been postulated, such as genetic factors, masticatory hyperfunction, trauma, and continued growth, but the underlying mechanism remains largely unknown. In this study, we investigated the potential role of mesenchymal stem cells (MSCs) derived from human MT in the pathogenesis of bone outgrowth. We demonstrated that MT harbored a distinct subpopulation of MSCs, with enhanced osteogenic and decreased adipogenic differentiation capacities, as compared with their counterparts from normal jaw bone. The increased osteogenic differentiation of mandibular torus MSCs was associated with the suppression of Notch3 signaling and its downstream target genes, Jag1 and Hey1, and a reciprocal increase in the transcriptional activation of ATF4 and NFATc1 genes. Targeted knockdown of Notch3 expression by transient siRNA transfection promoted the expression of osteogenic transcription factors in normal jaw bone MSCs. Our data suggest that the loss of Notch3 signaling may contribute partly to bone outgrowth in MT, as mediated by enhanced MSC-driven osteogenic differentiation in the jaw bone.
下颌隆突（MT）是位于下颌骨舌面的一种常见的口腔内骨性赘生物。组织学特征包括由成熟皮质骨和小梁骨组成的增生性骨。关于MT的病因已经提出了一些理论，如遗传因素、咀嚼功能亢进、创伤和持续生长，但潜在机制在很大程度上仍然未知。在本研究中，我们调查了源自人MT的间充质干细胞（MSC）在骨赘生物发病机制中的潜在作用。我们证明，与来自正常颌骨的MSC相比，MT含有一个独特的MSC亚群，其成骨能力增强而成脂分化能力降低。下颌隆突MSC成骨分化增加与Notch3信号及其下游靶基因Jag1和Hey1的抑制以及ATF4和NFATc1基因转录激活的相应增加有关。通过瞬时siRNA转染靶向敲低Notch3表达可促进正常颌骨MSC中成骨转录因子的表达。我们的数据表明，Notch3信号的缺失可能部分导致MT中的骨赘生物，这是由颌骨中MSC驱动的成骨分化增强介导的。
