title: Abnormal osteopontin and matrix extracellular phosphoglycoprotein localization, and odontoblast differentiation, in X-linked hypophosphatemic teeth.
abstract: Mutations in phosphate-regulating gene (PHEX) lead to X-linked hypophosphatemic rickets (XLH), a genetic disease characterized by impaired mineralization in bones and teeth. In human XLH tooth dentin, calcospherites that would normally merge as part of the mineralization process are separated by unmineralized interglobular spaces where fragments of matrix proteins accumulate. Here, we immunolocalized osteopontin (OPN) in human XLH teeth, in a three-dimensional XLH human dental pulp stem cell-collagen scaffold culture model and in a rat tooth injury repair model treated with acidic serine- and aspartate-rich motif peptides (ASARM). In parallel, matrix extracellular phosphoglycoprotein (MEPE) immunolocalization and alkaline phosphatase (ALP) activity were assessed in XLH teeth. OPN was expressed by odontoblasts in the XLH models, and localized to the abnormal calcospherites of XLH tooth dentin. In addition, ALP activity and MEPE localization were abnormal in human XLH teeth, with MEPE showing an accumulation in the unmineralized interglobular spaces in dentin. Furthermore, XLH odontoblasts failed to form a well-polarized odontoblast layer. These data suggest that both MEPE and OPN are involved in impaired tooth mineralization associated with XLH, possibly through different effects on the mineralization process.
authors.affiliation: EA 2496, Faculty of Dentistry , Paris Descartes University , France .
authors.forename: B
authors.initials: B
authors.lastname: Salmon
authors.forename: C
authors.initials: C
authors.lastname: Bardet
authors.forename: B R
authors.initials: BR
authors.lastname: Coyac
authors.forename: B
authors.initials: B
authors.lastname: Baroukh
authors.forename: J
authors.initials: J
authors.lastname: Naji
authors.forename: P S
authors.initials: PS
authors.lastname: Rowe
authors.forename: S
authors.initials: S
authors.lastname: Opsahl Vital
authors.forename: A
authors.initials: A
authors.lastname: Linglart
authors.forename: M D
authors.initials: MD
authors.lastname: Mckee
authors.forename: C
authors.initials: C
authors.lastname: Chaussain
mesh_terms: D000293:Adolescent; D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D053098:Familial Hypophosphatemic Rickets / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D009804:Odontoblasts / Q000166:cytology*; D053495:Osteopontin / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D014070:Tooth / Q000166:cytology / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D010750:Phosphoproteins; D053495:Osteopontin
keywords: Alkaline phosphatase; X-linked hypophosphatemia (XLH); acidic serine- and aspartate-rich motif (ASARM); dentin; matrix extracellular phosphoglycoprotein (MEPE); odontoblast; osteopontin