title: Distorted Patterns of Dentinogenesis and Eruption in Msx2 Null Mutants: Involvement of Sost/Sclerostin.
abstract: The muscle segment homeogenes Msx1 and Msx2 play a major role in tooth and bone formation. Periodontal osteoclast impairment also occurs in Msx2 null mutant mice, which is restored by overexpression of the receptor activator of NF-κB targeted in osteoclast lineage. Here, we investigated the role of Msx2 in dentinogenesis. Experiments were performed on Msx2(-/-) mice and the MDPC-23 odontoblastic cell line. After Msx2 gene silencing, real-time quantitative RT-PCR data showed significant overexpression of Runx2, Bglap, Dspp, and Alpl. Of three inhibitors of Wnt/β-catenin signaling (Dkk1, SostDc1, and Sost/Sclerostin), only Sost was expressed in postnatal teeth and overexpressed in Msx2(-/-) tooth samples. Initial crown dentin formation-primary dentinogenesis-occurred fairly normally in Msx2(-/-) teeth, albeit with distorted cusp patterns. Later stages of tooth development were characterized by a deviation from secondary toward tertiary dentinogenesis with osteodentin formation and impaired dentin deposition leading to limited root elongation. In Msx2(-/-)/receptor activator of NF-κB-transgenic double mutants, the dentin phenotype, notably in the roots, was rescued and sclerostin levels were normalized. These data suggest that Msx2 may act indirectly on dentinogenesis by controlling osteoclast activity and the signaling network related to eruption, supporting and further extending the concept that Msx2 controls formation of mineralized tissues by inhibition of the Wnt/β-catenin pathway; Sost in dentin and Dkk1 in bone, as previously demonstrated.
authors.affiliation: Molecular Oral Pathophysiology Team, Centre de Recherche des Cordeliers, INSERM UMRS 1138, Universities Paris-Diderot, Paris-Descartes and Pierre et Marie Curie, Paris, France.
authors.forename: Nawel
authors.initials: N
authors.lastname: Amri
authors.affiliation: Molecular Oral Pathophysiology Team, Centre de Recherche des Cordeliers, INSERM UMRS 1138, Universities Paris-Diderot, Paris-Descartes and Pierre et Marie Curie, Paris, France; Dental Service, Hospital la Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France; Faculty of Dentistry, University of Félix Houphouët Boigny, Abidjan, Côte d'Ivoire.
authors.forename: Stéphane X
authors.initials: SX
authors.lastname: Djolé
authors.affiliation: Molecular Oral Pathophysiology Team, Centre de Recherche des Cordeliers, INSERM UMRS 1138, Universities Paris-Diderot, Paris-Descartes and Pierre et Marie Curie, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Petit
authors.affiliation: Molecular Oral Pathophysiology Team, Centre de Recherche des Cordeliers, INSERM UMRS 1138, Universities Paris-Diderot, Paris-Descartes and Pierre et Marie Curie, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Babajko
authors.affiliation: Molecular Oral Pathophysiology Team, Centre de Recherche des Cordeliers, INSERM UMRS 1138, Universities Paris-Diderot, Paris-Descartes and Pierre et Marie Curie, Paris, France.
authors.forename: Amélie E
authors.initials: AE
authors.lastname: Coudert
authors.affiliation: Molecular Oral Pathophysiology Team, Centre de Recherche des Cordeliers, INSERM UMRS 1138, Universities Paris-Diderot, Paris-Descartes and Pierre et Marie Curie, Paris, France; Dental Service, Hospital la Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Castaneda
authors.affiliation: Molecular Oral Pathophysiology Team, Centre de Recherche des Cordeliers, INSERM UMRS 1138, Universities Paris-Diderot, Paris-Descartes and Pierre et Marie Curie, Paris, France; Dental Service, Hospital la Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Simon
authors.affiliation: Molecular Oral Pathophysiology Team, Centre de Recherche des Cordeliers, INSERM UMRS 1138, Universities Paris-Diderot, Paris-Descartes and Pierre et Marie Curie, Paris, France; Reference Centre, Buccal and Facial Rare Malformations, Rothschild Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. Electronic address: ariane.berdal@crc.jussieu.fr.
authors.forename: Ariane
authors.initials: A
authors.lastname: Berdal
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D003804:Dentin / Q000378:metabolism; D003810:Dentinogenesis / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D009804:Odontoblasts / Q000166:cytology; D010010:Osteoclasts / Q000166:cytology; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics* / Q000378:metabolism; D014070:Tooth / Q000254:growth & development; D014078:Tooth Eruption; D014092:Tooth Root / Q000254:growth & development; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006023:Glycoproteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C084119:MSX2 protein; D053246:Receptor Activator of Nuclear Factor-kappa B; C486030:Sost protein, mouse; D051176:beta Catenin