title: Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation.
abstract: Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP-PPR system during root morphogenesis and tooth eruption.
authors.affiliation: Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.|Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA.
authors.forename: Wanida
authors.initials: W
authors.lastname: Ono
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA.
authors.forename: Naoko
authors.initials: N
authors.lastname: Sakagami
authors.affiliation: Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nishimori
authors.affiliation: Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.|Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ono
authors.affiliation: Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Henry M
authors.initials: HM
authors.lastname: Kronenberg
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D003739:Dental Cementum / Q000166:cytology; D003795:Dental Sac / Q000166:cytology; D004843:Epistasis, Genetic; D017353:Gene Deletion; D006655:Histone Deacetylases / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D038081:Organogenesis; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D010641:Phenotype; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D000076182:Sp7 Transcription Factor; D014078:Tooth Eruption; D014092:Tooth Root / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D044162:Parathyroid Hormone-Related Protein; C082838:Postn protein, mouse; D044168:Receptor, Parathyroid Hormone, Type 1; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases