title: Inactivation of bone morphogenetic protein 1 (Bmp1) and tolloid-like 1 (Tll1) in cells expressing type I collagen leads to dental and periodontal defects in mice.
abstract: Bone morphogenetic protein 1 (BMP1) and tolloid-like 1 (TLL1) belong to the BMP1/tolloid-like proteinase family, which cleaves secretory proteins. The constitutive deletion of the Bmp1 or Tll1 genes causes perinatal or embryonic lethality in mice. In this study, we first studied the β-galactosidase activity in mice in which an IRES-lacZ-Neo cassette was inserted in the intron of either the Bmp1 or the Tll1 gene; the β-galactosidase activities were used to reflect the expression of endogenous Bmp1 and Tll1, respectively. Our X-gal staining results showed that the odontoblasts in the tooth and cells in the periodontal ligament express both Bmp1 and Tll1. We then created Bmp1flox/floxand Tll1flox/floxmice by removing the IRES-lacZ-Neo cassette. By breeding 2.3 kb Col1a1-Cre mice with the Bmp1flox/floxand Tll1flox/floxmice, we further generated Col1a1-Cre;Bmp1flox/flox;Tll1flox/floxmice in which both Bmp1 and Tll1 were inactivated in the Type I collagen-expressing cells. We employed X-ray radiography, histology and immunohistochemistry approaches to characterize the Col1a1-Cre;Bmp1flox/flox;Tll1flox/floxmice. Our results showed that the molars of the Col1a1-Cre;Bmp1flox/flox;Tll1flox/floxmice had wider predentin, thinner dentin and larger pulp chambers than those of the normal controls. The dentinal tubules of the molars in the Col1a1-Cre;Bmp1flox/flox;Tll1flox/floxmice appeared disorganized. The level of dentin sialophosphoprotein in the molars of the 6-week-old Col1a1-Cre;Bmp1flox/flox;Tll1flox/floxmice was lower than in the normal controls. The periodontal ligaments of the Col1a1-Cre;Bmp1flox/flox;Tll1flox/floxmice were disorganized and had less fibrillin-1. Our findings indicate that the proteinases encoded by Bmp1 and Tll1 genes play essential roles in the development and maintenance of mouse dentin and periodontal ligaments.
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M College of Dentistry, 3302 Gaston Ave., Dallas, TX, 75246, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M College of Dentistry, 3302 Gaston Ave., Dallas, TX, 75246, USA.
authors.forename: Priyam
authors.initials: P
authors.lastname: Jani
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M College of Dentistry, 3302 Gaston Ave., Dallas, TX, 75246, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Liang
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M College of Dentistry, 3302 Gaston Ave., Dallas, TX, 75246, USA. ylu@tamhsc.edu.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M College of Dentistry, 3302 Gaston Ave., Dallas, TX, 75246, USA. cqin@tamhsc.edu.
authors.forename: Chunlin
authors.identifier: http://orcid.org/0000-0002-2906-9074
authors.initials: C
authors.lastname: Qin
mesh_terms: D000818:Animals; D055395:Bone Morphogenetic Protein 1 / Q000172:deficiency / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism*; D003804:Dentin / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D051379:Mice; D008963:Molar / Q000473:pathology; D009804:Odontoblasts / Q000378:metabolism; D010513:Periodontal Ligament / Q000473:pathology*; D010750:Phosphoproteins / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism; D055394:Tolloid-Like Metalloproteinases / Q000172:deficiency*; D000099311:Dentin Sialophosphoprotein
chemical_list: D055395:Bone Morphogenetic Protein 1; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D055394:Tolloid-Like Metalloproteinases; D000099311:Dentin Sialophosphoprotein; C484477:Tll1 protein, mouse; C525707:Bmp1 protein, mouse
keywords: Bone morphogenetic protein 1; Knockout mice; Periodontium; Tolloid-like 1; Tooth; Type I collagen