title: Loss of Notch3 Signaling Enhances Osteogenesis of Mesenchymal Stem Cells from Mandibular Torus.
abstract: 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.
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.
authors.forename: X W
authors.initials: XW
authors.lastname: Dou
authors.affiliation: 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.
authors.forename: W
authors.initials: W
authors.lastname: Park
authors.affiliation: 3 Department of Endodontics, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.
authors.forename: Q Z
authors.initials: QZ
authors.lastname: Zhang
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.|4 Department of Oral and Maxillofacial Surgery, Penn Medicine Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: L R
authors.initials: LR
authors.lastname: Carrasco
authors.affiliation: 1 Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.|4 Department of Oral and Maxillofacial Surgery, Penn Medicine Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Le
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002454:Cell Differentiation; D005096:Exostoses / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008334:Mandible / Q000002:abnormalities*; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D008875:Middle Aged; D010012:Osteogenesis / Q000502:physiology*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D000071656:Receptor, Notch3 / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: C499374:NOTCH3 protein, human; D034741:RNA, Small Interfering; D000071656:Receptor, Notch3
keywords: adult stem cell(s); bone formation; cell signaling; gene expression; jaw bone anomalies; oral and maxillofacial surgery