title: Cementogenic genes in human periodontal ligament stem cells are downregulated in response to osteogenic stimulation while upregulated by vitamin C treatment.
abstract: Regeneration of periodontal tissues, particularly cementum, is key to regaining periodontal attachment and health. Human periodontal ligament stem cells (hPDLSCs) have been shown to be a good cell source to regenerate periodontal tissues. However, their subpopulations and the differentiation induction in relation to cementogenic lineages is unclear. Thus, we aim to examine the expression of cementum-associated genes in PDLSC subpopulations and determine the effect of broadly used osteogenic stimulus or vitamin C (VC) on the expression of cementogenic and osteogenic genes in PDLSCs. Our real-time quantitative polymerase chain reaction (qPCR) analysis showed that cementogenic marker cementum attachment protein (CAP) expressed only slightly higher in STRO-1+/CD146+, STRO-1-/CD146+and STRO-1-/CD146-subpopulations than in the original cell pool, while cementum protein 1 (CEMP1) expression in these subpopulations was not different from the original pool. Notably, under the stimulation with osteogenic differentiation medium, CAP and CEMP1 were downregulated while osteogenic markers bone sialoprotein (BSP) and osteocalcin (OCN) were upregulated. Both CAP and CEMP1 were upregulated by VC treatment. Transplantation of VC-treated PDLSCs into immunocompromised mice resulted in forming significantly more ectopic cementum- and bone-like mineral tissues in vivo. Immunohistochemical analysis of the ectopic growth showed that CAP and CEMP1 were mainly expressed in the mineral tissue and in some cells of the fibrous tissues. We conclude that osteogenic stimulation is not inductive but appears to be inhibitory of cementogenic pathways, whereas VC induces cementogenic lineage commitment by PDLSCs and may be a useful stimulus for cementogenesis in periodontal regeneration.
authors.affiliation: Department of Endodontics, Henry M. Goldman School of Dental Medicine, Boston University, Boston, MA, 02118, USA.|Faculté de médecine dentaire, Département d'endodontie, Université Laval, Québec, QC, G1V 0A6, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gauthier
authors.affiliation: Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors.forename: Zongdong
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38105, USA.
authors.forename: Quynh T
authors.initials: QT
authors.lastname: Tran
authors.affiliation: Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors.forename: Fazal-Ur-Rehman
authors.initials: FU
authors.lastname: Bhatti
authors.affiliation: Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.|VIP Dental Service and Geriatric Dentistry, School and Hospital of Stomatology, Peking University, Beijing, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Endodontics, Henry M. Goldman School of Dental Medicine, Boston University, Boston, MA, 02118, USA. gtjhuang@uthsc.edu.|Faculté de médecine dentaire, Département d'endodontie, Université Laval, Québec, QC, G1V 0A6, Canada. gtjhuang@uthsc.edu.|Lab, Cancer Research Building, University of Tennessee Health Science Center, 19 S. Manassas St. Lab Rm 225, Office 222, Memphis, TN, 38163, USA. gtjhuang@uthsc.edu.
authors.forename: George T-J
authors.initials: GT
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D025021:Cementogenesis / Q000235:genetics*; D003739:Dental Cementum / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics*; D010513:Periodontal Ligament / Q000166:cytology*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C510886:CEMP1 protein, human; D011506:Proteins; D000469:Alkaline Phosphatase; C404489:HACD1 protein, human; D017027:Protein Tyrosine Phosphatases; D001205:Ascorbic Acid
keywords: Cementum attachment protein; Cementum protein 1; Osteogenic induction; Periodontal ligament stem cells; Vitamin C