title: Uremia Induces Dental Pulp Ossification but Reciprocally Inhibits Adjacent Alveolar Bone Osteogenesis.
abstract: Uremic patients are predisposed to atrophy of the alveolar bone and narrowing of the dental pulp chamber. Such pulp chamber changes have only been diagnosed radiologically; however, this has not been supported by any pathological evidence. We used a uremic rat model with secondary hyperparathyroidism induced by 5/6 nephrectomy surgery and high-phosphate diet to examine the dental pulp and adjacent alveolar bone pathology. In addition, we collected pulp tissues for real-time PCR. We found an opposite histopathological presentation of the ossified dental pulp and the osteomalacic adjacent alveolar bone. Furthermore, pulp cells with positive staining for Thy-1, a surrogate stem cell marker, were significantly reduced in the pulp of uremic rats compared to the controls, indicating a paucity of stem cells. This was further evidenced by the reduced pulp expression of dickkopf-1 (Dkk-1), a Wnt/β-catenin signaling inhibitor produced by mesenchymal stem cells. In contrast, expressions of receptor activator of nuclear factor κB ligand (RANKL) and RANK in uremic pulp were up-regulated, probably to counteract the ossifying process of uremic pulp. In conclusion, uremic pulp ossifications were associated with a paucity of stem cells and dysregulated Dkk-1 and RANKL signaling systems, further shifting the imbalance toward osteogenesis. Strategies to counteract such an imbalance may offer a potential therapeutic target to improve dental health in uremic patients, which warrants further interventional studies.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Yang
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Zee-Fen
authors.initials: ZF
authors.lastname: Chang
authors.affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
authors.forename: Yat-Pang
authors.initials: YP
authors.lastname: Chau
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ann
authors.initials: A
authors.lastname: Chen
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. DAV47@tpech.gov.tw.|School of Medicine, National Yang-Ming University, Taipei, Taiwan. DAV47@tpech.gov.tw.|Department of Orthopedic Surgery, Taipei City Hospital, No. 10, Sect. 4, Ren-Ai Road, Da-An District, Taipei, 10629, Taiwan. DAV47@tpech.gov.tw.|Departments of Medical Research and Orthopedic Surgery, Taipei Veterans General Hospital, Taipei, Taiwan. DAV47@tpech.gov.tw.|Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan. DAV47@tpech.gov.tw.
authors.forename: Oscar Kuang-Sheng
authors.initials: OK
authors.lastname: Lee
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. ahyang@vghtpe.gov.tw.|School of Medicine, National Yang-Ming University, Taipei, Taiwan. ahyang@vghtpe.gov.tw.|Department of Pathology, Taipei Veterans General Hospital, No. 201, Sect. 2, Shih-Pai Road, Beitou District, Taipei, 11217, Taiwan. ahyang@vghtpe.gov.tw.
authors.forename: An-Hang
authors.initials: AH
authors.lastname: Yang
mesh_terms: D016301:Alveolar Bone Loss / Q000209:etiology*; D000539:Alveolar Process / Q000473:pathology*; D000818:Animals; D015519:Bone Density; D003782:Dental Pulp / Q000473:pathology*; D004195:Disease Models, Animal; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D009999:Ossification, Heterotopic / Q000209:etiology*; D010012:Osteogenesis / Q000502:physiology; D053245:RANK Ligand / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000473:pathology; D014511:Uremia / Q000150:complications*; D055114:X-Ray Microtomography
chemical_list: C531384:Dkk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D053245:RANK Ligand
keywords: Dickkopf-1; Osteomalacia; Pulp ossification; RANKL; Stem cells; Uremia