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Uremia Induces Dental Pulp Ossification but Reciprocally Inhibits Adjacent Alveolar Bone Osteogenesis

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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.

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Acknowledgments

This study was supported by the National Science Council, Taipei, Taiwan (NSC 99-2320-B-075-002-MY3); and the Taipei Veterans General Hospital, Taipei, Taiwan (VGH-100-B-020 and VGH-102-B-032).

Conflict of Interest

Chih-Yu Yang, Zee-Fen Chang, Yat-Pang Chau, Ann Chen, Oscar Kuang-Sheng Lee, and An-Hang Yang declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All animal experiments were approved by the Institutional Animal Care and Use Committee of Taipei Veterans General Hospital (Permit Number 2011-023).

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Authors and Affiliations

  1. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

    Chih-Yu Yang, Oscar Kuang-Sheng Lee & An-Hang Yang

  2. School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Chih-Yu Yang, Oscar Kuang-Sheng Lee & An-Hang Yang

  3. Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Chih-Yu Yang

  4. Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan

    Zee-Fen Chang

  5. Department of Medicine, Mackay Medical College, New Taipei City, Taiwan

    Yat-Pang Chau

  6. Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

    Ann Chen

  7. Department of Orthopedic Surgery, Taipei City Hospital, No. 10, Sect. 4, Ren-Ai Road, Da-An District, Taipei, 10629, Taiwan

    Oscar Kuang-Sheng Lee

  8. Departments of Medical Research and Orthopedic Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    Oscar Kuang-Sheng Lee

  9. Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan

    Oscar Kuang-Sheng Lee

  10. Department of Pathology, Taipei Veterans General Hospital, No. 201, Sect. 2, Shih-Pai Road, Beitou District, Taipei, 11217, Taiwan

    An-Hang Yang

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  1. Chih-Yu Yang
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Correspondence to Oscar Kuang-Sheng Lee or An-Hang Yang.

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Yang, CY., Chang, ZF., Chau, YP. et al. Uremia Induces Dental Pulp Ossification but Reciprocally Inhibits Adjacent Alveolar Bone Osteogenesis. Calcif Tissue Int 97, 466–475 (2015). https://doi.org/10.1007/s00223-015-0030-5

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