title: BMP1 and TLL1 Are Required for Maintaining Periodontal Homeostasis.
abstract: Mutations in bone morphogenetic protein 1 (BMP1) in humans or deletion of BMP1 and related protease tolloid like 1 (TLL1) in mice lead to osteogenesis imperfecta (OI). Here, we show progressive periodontal defects in mice in which both BMP1 and TLL1 have been conditionally ablated, including malformed periodontal ligament (PDL) (recently shown to play key roles in normal alveolar bone formation), significant loss in alveolar bone mass ( P < 0.01), and a sharp reduction in cellular cementum. Molecular mechanism studies revealed a dramatic increase in the uncleaved precursor of type I collagen (procollagen I) and a reduction in dentin matrix protein 1 (DMP1), which is partially responsible for defects in extracellular matrix (ECM) formation and mineralization. We also showed a marked increase in the expression of matrix metallopeptidase 13 (MMP13) and tartrate-resistant acid phosphatase (TRAP), leading to an acceleration in periodontal breakdown. Finally, we demonstrated that systemic application of antibiotics significantly improved the alveolar bone and PDL damage of the knockdown phenotype, which are thus shown to be partially secondary to pathogen-induced inflammation. Together, identification of the novel roles of BMP1 and TLL1 in maintaining homeostasis of periodontal formation, partly via biosynthetic processing of procollagen I and DMP1, provides novel insights into key contributions of the extracellular matrix environment to periodontal homeostasis and contributes toward understanding of the pathology of periodontitis.
authors.affiliation: 1 Biomedical Sciences, Texas A&M College of Dentistry, Dallas, TX, USA.|2 State Key Laboratory of Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: 3 Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
authors.forename: D
authors.initials: D
authors.lastname: Massoudi
authors.affiliation: 1 Biomedical Sciences, Texas A&M College of Dentistry, Dallas, TX, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ren
authors.affiliation: 3 Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Muir
authors.affiliation: 4 Department of Periodontics, UT Health Science Center School of Dentistry, San Antonio, TX, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Harris
authors.affiliation: 3 Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Greenspan
authors.affiliation: 1 Biomedical Sciences, Texas A&M College of Dentistry, Dallas, TX, USA.
authors.forename: J Q
authors.initials: JQ
authors.lastname: Feng
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D055395:Bone Morphogenetic Protein 1 / Q000172:deficiency / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D006706:Homeostasis; D007150:Immunohistochemistry; D008334:Mandible; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010513:Periodontal Ligament / Q000502:physiology*; D010518:Periodontitis / Q000503:physiopathology*; D010641:Phenotype; D011347:Procollagen / Q000096:biosynthesis; D000071681:Tartrate-Resistant Acid Phosphatase / Q000378:metabolism; D055394:Tolloid-Like Metalloproteinases / Q000172:deficiency / Q000502:physiology*; D055114:X-Ray Microtomography
chemical_list: D000900:Anti-Bacterial Agents; C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; D011347:Procollagen; D000071681:Tartrate-Resistant Acid Phosphatase; D055394:Tolloid-Like Metalloproteinases; D053509:Matrix Metalloproteinase 13; C484477:Tll1 protein, mouse; D055395:Bone Morphogenetic Protein 1
keywords: ECM; craniofacial biology/genetics; inflammation; matrix biology; mineralized tissue/development; periodontal tissues/periodontium