title: Deficiency in acellular cementum and periodontal attachment in bsp null mice.
abstract: Bone sialoprotein (BSP) is an extracellular matrix protein found in mineralized tissues of the skeleton and dentition. BSP is multifunctional, affecting cell attachment and signaling through an RGD integrin-binding region, and acting as a positive regulator for mineral precipitation by nucleating hydroxyapatite crystals. BSP is present in cementum, the hard tissue covering the tooth root that anchors periodontal ligament (PDL) attachment. To test our hypothesis that BSP plays an important role in cementogenesis, we analyzed tooth development in a Bsp null ((-/-)) mouse model. Developmental analysis by histology, histochemistry, and SEM revealed a significant reduction in acellular cementum formation on Bsp                 (-/-) mouse molar and incisor roots, and the cementum deposited appeared hypomineralized. Structural defects in cementum-PDL interfaces in Bsp                 (-/-) mice caused PDL detachment, likely contributing to the high incidence of incisor malocclusion. Loss of BSP caused progressively disorganized PDL and significantly increased epithelial down-growth with aging. Bsp                 (-/-) mice displayed extensive root and alveolar bone resorption, mediated by increased RANKL and the presence of osteoclasts. Results collected here suggest that BSP plays a non-redundant role in acellular cementum formation, likely involved in initiating mineralization on the root surface. Through its importance to cementum integrity, BSP is essential for periodontal function.
authors.affiliation: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. brian.foster@nih.gov
authors.forename: B L
authors.initials: BL
authors.lastname: Foster
authors.forename: Y
authors.initials: Y
authors.lastname: Soenjaya
authors.forename: F H
authors.initials: FH
authors.lastname: Nociti
authors.forename: E
authors.initials: E
authors.lastname: Holm
authors.forename: P M
authors.initials: PM
authors.lastname: Zerfas
authors.forename: H F
authors.initials: HF
authors.lastname: Wimer
authors.forename: D W
authors.initials: DW
authors.lastname: Holdsworth
authors.forename: J E
authors.initials: JE
authors.lastname: Aubin
authors.forename: G K
authors.initials: GK
authors.lastname: Hunter
authors.forename: H A
authors.initials: HA
authors.lastname: Goldberg
authors.forename: M J
authors.initials: MJ
authors.lastname: Somerman
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis; D016301:Alveolar Bone Loss / Q000473:pathology; D000818:Animals; D025021:Cementogenesis / Q000502:physiology*; D003739:Dental Cementum / Q000473:pathology*; D003804:Dentin / Q000648:ultrastructure; D004848:Epithelium / Q000473:pathology; D007180:Incisor / Q000648:ultrastructure; D058574:Integrin-Binding Sialoprotein / Q000235:genetics / Q000502:physiology*; D007633:Keratins / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D008963:Molar / Q000648:ultrastructure; D009805:Odontogenesis / Q000235:genetics / Q000502:physiology; D010010:Osteoclasts / Q000473:pathology; D053495:Osteopontin / Q000032:analysis; D017622:Periodontal Attachment Loss / Q000473:pathology; D010513:Periodontal Ligament / Q000473:pathology; D053245:RANK Ligand / Q000032:analysis; D012391:Root Resorption / Q000473:pathology; D014074:Tooth Calcification / Q000235:genetics / Q000502:physiology; D019237:Tooth Cervix / Q000648:ultrastructure; D055114:X-Ray Microtomography
chemical_list: C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; D053245:RANK Ligand; C506896:Spp1 protein, mouse; C505689:Tnfsf11 protein, mouse; D053495:Osteopontin; D007633:Keratins; D000469:Alkaline Phosphatase