RESUMEN
Runt-related transcription factor 2 (RUNX2) is well-known for its role in bone development and tooth morphogenesis. Most RUNX2 mutations described in the literature result in loss-of-function mutations of RUNX2 responsible for cleidocranial dysplasia, an autosomal dominant disorder. We describe here the oro-dental phenotype of four patients of a unique family with a 285â¯kb duplication including the entire sequence of RUNX2, likely responsible for three functional copies of the gene, leading to an increased RUNX2 dosage. Several dental anomalies of number (hypodontia or oligodontia), morphology (microdontia, radiculomegaly, taurodontism or dens invaginatus) and tooth position (rotation) were found in these patients.
Asunto(s)
Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Duplicación de Gen , Fenotipo , Anomalías Dentarias/genética , Adolescente , Adulto , Niño , Femenino , Dosificación de Gen , Humanos , Masculino , Linaje , Anomalías Dentarias/patologíaRESUMEN
Osteoporosis is characterized by low bone mineral density (BMD) and fragility fracture and affects over 200 million people worldwide. Bone quality describes the material properties that contribute to strength independently of BMD, and its quantitative analysis is a major priority in osteoporosis research. Tissue mineralization is a fundamental process requiring calcium and phosphate transporters. Here we identify impaired bone quality and strength in Slc20a2-/- mice lacking the phosphate transporter SLC20A2. Juveniles had abnormal endochondral and intramembranous ossification, decreased mineral accrual, and short stature. Adults exhibited only small reductions in bone mass and mineralization but a profound impairment of bone strength. Bone quality was severely impaired in Slc20a2-/- mice: yield load (-2.3 SD), maximum load (-1.7 SD), and stiffness (-2.7 SD) were all below values predicted from their bone mineral content as determined in a cohort of 320 wild-type controls. These studies identify Slc20a2 as a physiological regulator of tissue mineralization and highlight its critical role in the determination of bone quality and strength. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
Asunto(s)
Huesos/fisiología , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo III/genética , Animales , Animales Recién Nacidos , Desarrollo Óseo , Resorción Ósea/fisiopatología , Huesos/diagnóstico por imagen , Calcificación Fisiológica , Calcinosis/diagnóstico por imagen , Calcinosis/genética , Células Cultivadas , Condrocitos/metabolismo , Humanos , Incisivo/ultraestructura , Ratones Endogámicos C57BL , Ratones Noqueados , Osteoblastos/metabolismo , Fenotipo , Cráneo/diagnóstico por imagen , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo III/deficiencia , Diente/crecimiento & desarrollo , Microtomografía por Rayos XRESUMEN
Phosphate is a key component of dental mineral composition. The physiological role of membrane proteins of dental cells is suspected to be crucial for mineralization mechanisms. Contrary to published data related to calcium, data on regulation of phosphate flux through membrane of mineralizing cells are scarce. To address this lack of data, we studied the expression of six membranous phosphate transporters in two dental cell lines: a rat odontoblastic cell line (M2H4) and a mouse ameloblastic cell line (ALC) for which we optimized the mineralizing culture conditions.