Enzyme Replacement Therapy Prevents Dental Defects in a Model of Hypophosphatasia
Open Access
- 6 January 2011
- journal article
- research article
- Published by SAGE Publications in Journal of Dental Research
- Vol. 90 (4), 470-476
- https://doi.org/10.1177/0022034510393517
Abstract
Hypophosphatasia (HPP) occurs from loss-of-function mutation in the tissue-non-specific alkaline phosphatase (TNALP) gene, resulting in extracellular pyrophosphate accumulation that inhibits skeletal and dental mineralization. TNALP-null mice ( Akp2 -/-) phenocopy human infantile hypophosphatasia; they develop rickets at 1 week of age, and die before being weaned, having severe skeletal and dental hypomineralization and episodes of apnea and vitamin B6-responsive seizures. Delay and defects in dentin mineralization, together with a deficiency in acellular cementum, are characteristic. We report the prevention of these dental abnormalities in Akp2 -/- mice receiving treatment from birth with daily injections of a mineral-targeting, human TNALP (sALP-FcD10). sALP-FcD10 prevented hypomineralization of alveolar bone, dentin, and cementum as assessed by micro-computed tomography and histology. Osteopontin – a marker of acellular cementum – was immuno-localized along root surfaces, confirming that acellular cementum, typically missing or reduced in Akp2 -/- mice, formed normally. Our findings provide insight concerning how acellular cementum is formed on tooth surfaces to effect periodontal ligament attachment to retain teeth in their osseous alveolar sockets. Furthermore, they provide evidence that this enzyme-replacement therapy, applied early in post-natal life – where the majority of tooth root development occurs, including acellular cementum formation – could prevent the accelerated tooth loss seen in individuals with HPP.Keywords
This publication has 32 references indexed in Scilit:
- Genetic Etiology and Dental Pulp Cell Deficiency of HypophosphatasiaJournal of Dental Research, 2010
- Modulation of Calcium Oxalate Dihydrate Growth by Selective Crystal-face Binding of Phosphorylated Osteopontin and Polyaspartate Peptide Showing Occlusion by Sectoral (Compositional) ZoningPublished by Elsevier BV ,2009
- Enzyme Replacement Therapy for Murine HypophosphatasiaJournal of Bone and Mineral Research, 2008
- Hypophosphatasia affecting the permanent dentitionJournal of Oral Pathology & Medicine, 1996
- Localization and Expression of Osteopontin in Mineralized and Nonmineralized Tissues of the PeriodontiumaAnnals of the New York Academy of Sciences, 1995
- Postembedding colloidal‐gold immunocytochemistry of noncollagenous extracellular matrix proteins in mineralized tissuesMicroscopy Research and Technique, 1995
- Immunolocalization of osteopontin, osteocalcin, and dentin sialoprotein during dental root formation and early cementogenesis in the ratJournal of Bone and Mineral Research, 1994
- Ultrastructural immunolocalization of noncollagenous (osteopontin and osteocalcin) and plasma (albumin and α2HS-glycoprotein) proteins in rat boneJournal of Bone and Mineral Research, 1993
- Effects of fixation and demineralization on the retention of bone phosphoprotein and other matrix components as evaluated by biochemical analyses and quantitative immunocytochemistryJournal of Bone and Mineral Research, 1991
- Permanent teeth in hypophosphatasia: light and electron microscopic studyJournal of Oral Pathology & Medicine, 1991