title: Heritability of periodontal bone loss in mice.
abstract: BACKGROUND
  Periodontitis is an inflammatory disease of the periodontal tissues that compromises tooth support and can lead to tooth loss. Although bacterial biofilm is central in disease pathogenesis, the host response plays an important role in the progression and severity of periodontitis. Indeed, clinical genetic studies indicate that periodontitis is 50% heritable. In this study, we hypothesized that lipopolysaccharide (LPS) injections lead to a strain-dependent periodontal bone loss pattern.
  
  
  METHODS
  We utilized five inbred mouse strains that derive the recombinant strains of the hybrid mouse diversity panel. Mice received Porphyromonas gingivalis-LPS injections for 6 wk.
  
  
  CONCLUSIONS
  Micro-computed tomography analysis demonstrated a statistically significant strain-dependent bone loss. The most susceptible strain, C57BL/6J, had a fivefold higher LPS-induced bone loss compared to the most resistant strain, A/J. More importantly, periodontal bone loss revealed 49% heritability, which closely mimics periodontitis heritability for patients. To evaluate further the functional differences that underlie periodontal bone loss, osteoclast numbers of C57BL/6J and A/J mice were measured in vivo and in vitro. In vitro analysis of osteoclastogenic potential showed a higher number of osteoclasts in C57BL/6J compared to A/J mice. In vivo LPS injections statistically significantly increased osteoclast numbers in both groups. Importantly, the number of osteoclasts was higher in C57BL/6J vs. A/J mice. These data support a significant role of the genetic framework in LPS-induced periodontal bone loss and the feasibility of utilizing the hybrid mouse diversity panel to determine the genetic factors that affect periodontal bone loss. Expanding these studies will contribute in predicting patients genetically predisposed to periodontitis and in identifying the biological basis of disease susceptibility.
authors.affiliation: School of Dentistry, Section of Periodontics, University of California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hiyari
authors.affiliation: School of Dentistry, Section of Oral and Maxillofacial Radiology, University of California, Los Angeles, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Atti
authors.affiliation: School of Dentistry, Section of Periodontics, University of California, Los Angeles, CA, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Camargo
authors.affiliation: Department of Computer Sciences, University of California, Los Angeles, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Eskin
authors.affiliation: David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Lusis
authors.affiliation: School of Dentistry, Section of Oral and Maxillofacial Radiology, University of California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tetradis
authors.affiliation: School of Dentistry, Section of Periodontics, University of California, Los Angeles, CA, USA.
authors.forename: F Q
authors.initials: FQ
authors.lastname: Pirih
mesh_terms: D016301:Alveolar Bone Loss / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000302:isolation & purification; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010518:Periodontitis / Q000139:chemically induced / Q000150:complications* / Q000235:genetics*; D016966:Porphyromonas gingivalis / Q000737:chemistry
chemical_list: D008070:Lipopolysaccharides
keywords: alveolar bone; animal model; genome; lipopolysaccharide