Title :

Defective Mineralization in X-Linked Hypophosphatemia Dental Pulp Cell Cultures

Author(s) :

Coyac, B.R. [Auteur]
Hoac, B. [Auteur]
Chafey, P. [Auteur]
Université Paris Descartes - Faculté de Médecine [UPD5 Médecine]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Falgayrac, Guillaume [Auteur]
Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 [MABLab]
Université de Lille
Slimani, L. [Auteur]
Pathologies, imagerie et biothérapies oro-faciales = Orofacial pathologies, imaging and biotherapies [URP 2496]
Rowe, P.S. [Auteur]
Penel, G. [Auteur]
Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 [MABLab]
Linglart, A. [Auteur]
Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre]
Mckee, M.D. [Auteur]
McGill University = Université McGill [Montréal, Canada]
Chaussain, C. [Auteur]
Service d'Odontologie [Bretonneau]
Bardet, C. [Auteur]
Pathologies, imagerie et biothérapies oro-faciales = Orofacial pathologies, imaging and biotherapies [URP 2496]

Journal title :

Journal of dental research

Pages :

184-191

Publisher :

SAGE Publications (UK and US)

Publication date :

2017-09-07

ISSN :

0022-0345

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

X-linked hypophosphatemia (XLH) is a skeletal disease caused by inactivating mutations in the PHEX gene. Mutated or absent PHEX protein/enzyme leads to a decreased serum phosphate level, which cause mineralization defects ...
Show more >X-linked hypophosphatemia (XLH) is a skeletal disease caused by inactivating mutations in the PHEX gene. Mutated or absent PHEX protein/enzyme leads to a decreased serum phosphate level, which cause mineralization defects in the skeleton and teeth (osteomalacia/odontomalacia). It is not yet altogether clear whether these manifestations are caused solely by insufficient circulating phosphate availability for mineralization or also by a direct, local intrinsic effect caused by impaired PHEX activity. Here, we evaluated the local role of PHEX in a 3-dimensional model of extracellular matrix (ECM) mineralization. Dense collagen hydrogels were seeded either with human dental pulp cells from patients with characterized PHEX mutations or with sex- and age-matched healthy controls and cultured up to 24 d using osteogenic medium with standard phosphate concentration. Calcium quantification, micro–computed tomography, and histology with von Kossa staining for mineral showed significantly lower mineralization in XLH cell-seeded scaffolds, using nonparametric statistical tests. While apatitic mineralization was observed along collagen fibrils by electron microscopy in both groups, Raman microspectrometry indicated that XLH cells harboring the PHEX mutation produced less mineralized scaffolds having impaired mineral quality with less carbonate substitution and lower crystallinity. In the XLH cultures, immunoblotting revealed more abundant osteopontin (OPN), dentin matrix protein 1 (DMP1), and matrix extracellular phosphoglycoprotein (MEPE) than controls, as well as the presence of fragments of these proteins not found in controls, suggesting a role for PHEX in SIBLING protein degradation. Immunohistochemistry revealed altered OPN and DMP1 associated with an increased alkaline phosphatase staining in the XLH cultures. These results are consistent with impaired PHEX activity having local ECM effects in XLH. Future treatments for XLH should target both systemic and local manifestations.Show less >

Language :

Français

Popular science :

Non

Collections :

• Marrow Adiposity & Bone Lab (MABLab) - ULR 4490

Source :

Harvested from HAL