title: Msx1 role in craniofacial bone morphogenesis.
abstract: The homeobox gene Msx1 encodes a transcription factor that is highly expressed during embryogenesis and postnatal development in bone. Mutations of the MSX1 gene in humans are associated with cleft palate and (or) tooth agenesis. A similar phenotype is observed in newborn mice invalidated for the Msx1 gene. However, little is known about Msx1 function in osteoblast differentiation and bone mineralization in vivo. In the present study, we aimed to explore the variations of individualized bone shape in a subtle way avoiding the often severe consequences associated with gene mutations. We established transgenic mice that specifically express Msx1 in mineral-matrix-secreting cells under the control of the mouse 2.3kb collagen 1 alpha 1 (Col1α1) promoter, which enabled us to investigate Msx1 function in bone in vivo. Adult transgenic mice (Msx1-Tg) presented altered skull shape and mineralization resulting from increased Msx1 expression during bone development. Serial section analysis of the mandibles showed a high amount of bone matrix in these mice. In addition, osteoblast number, cell proliferation and apoptosis were higher in Msx1-Tg mice than in controls with regional differences that could account for alterations of bone shape. However, Von Kossa staining and μCT analysis showed that bone mineralization was lower in Msx1-Tg mice than in controls due to alteration of osteoblastic differentiation. Msx1 appears to act as a modeling factor for membranous bone; it stimulates trabecular bone metabolism but limits cortical bone growth by promoting apoptosis, and concomitantly controls the collagen-based mineralization process.
authors.affiliation: Cordeliers Research Center, INSERM UMRS 1138, Laboratory of Molecular Oral Pathophysiology, 15 rue de l'école de médecine, Paris, F-75006, France; Paris-Descartes University, Paris, F-75006, France; Pierre and Marie Curie University, Paris, F-75006, France; Paris-Diderot University, UFR Odontology, Paris, F-75006, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Nassif
authors.affiliation: Cordeliers Research Center, INSERM UMRS 1138, Laboratory of Molecular Oral Pathophysiology, 15 rue de l'école de médecine, Paris, F-75006, France; Paris-Descartes University, Paris, F-75006, France; Pierre and Marie Curie University, Paris, F-75006, France; Paris-Diderot University, UFR Odontology, Paris, F-75006, France.
authors.forename: Ibtisam
authors.initials: I
authors.lastname: Senussi
authors.affiliation: Cordeliers Research Center, INSERM UMRS 1138, Laboratory of Molecular Oral Pathophysiology, 15 rue de l'école de médecine, Paris, F-75006, France; Paris-Descartes University, Paris, F-75006, France; Pierre and Marie Curie University, Paris, F-75006, France; Paris-Diderot University, UFR Odontology, Paris, F-75006, France.
authors.forename: Fleur
authors.initials: F
authors.lastname: Meary
authors.affiliation: Cordeliers Research Center, INSERM UMRS 1138, Laboratory of Molecular Oral Pathophysiology, 15 rue de l'école de médecine, Paris, F-75006, France; Paris-Descartes University, Paris, F-75006, France; Pierre and Marie Curie University, Paris, F-75006, France; Paris-Diderot University, UFR Odontology, Paris, F-75006, France.
authors.forename: Sophia
authors.initials: S
authors.lastname: Loiodice
authors.affiliation: Cordeliers Research Center, INSERM UMRS 1138, Laboratory of Molecular Oral Pathophysiology, 15 rue de l'école de médecine, Paris, F-75006, France; Paris-Descartes University, Paris, F-75006, France; Pierre and Marie Curie University, Paris, F-75006, France; Paris-Diderot University, UFR Odontology, Paris, F-75006, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Hotton
authors.affiliation: Pasteur Institute, URA CNRS 2578, 25 rue du Docteur Roux, Paris, F-75724, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Robert
authors.affiliation: Lariboisière-Saint-Louis Medical School, 10 Avenue de Verdun, Paris, F-75010, France.
authors.forename: Morad
authors.initials: M
authors.lastname: Bensidhoum
authors.affiliation: Cordeliers Research Center, INSERM UMRS 1138, Laboratory of Molecular Oral Pathophysiology, 15 rue de l'école de médecine, Paris, F-75006, France; Paris-Descartes University, Paris, F-75006, France; Pierre and Marie Curie University, Paris, F-75006, France; Paris-Diderot University, UFR Odontology, Paris, F-75006, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Berdal
authors.affiliation: Cordeliers Research Center, INSERM UMRS 1138, Laboratory of Molecular Oral Pathophysiology, 15 rue de l'école de médecine, Paris, F-75006, France; Paris-Descartes University, Paris, F-75006, France; Pierre and Marie Curie University, Paris, F-75006, France; Paris-Diderot University, UFR Odontology, Paris, F-75006, France. Electronic address: sylvie.babajko@crc.jussieu.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Babajko
mesh_terms: D000818:Animals; D001857:Bone Matrix / Q000378:metabolism; D002113:Calcification, Physiologic; D019070:Cell Lineage; D051957:MSX1 Transcription Factor / Q000378:metabolism*; D008334:Mandible / Q000033:anatomy & histology; D008822:Mice, Transgenic; D009024:Morphogenesis; D010012:Osteogenesis; D012886:Skull / Q000033:anatomy & histology / Q000254:growth & development*; D019076:Transgenes
chemical_list: D051957:MSX1 Transcription Factor; C484084:Msx1 protein, mouse
keywords: Animal model; Bone; Collagen; Mineralization; Msx1; Osteoblast