title: A novel ex vivo culture model for inflammatory bone destruction.
abstract: Pathological alterations in the balance of bone metabolism are central to the progression of inflammatory bone diseases such as periodontal disease. We have developed and characterized a novel ex vivo murine mandible model of inflammatory bone destruction. Slices of mandible were cultured for 14 days in the presence or absence of P. gingivalis lipopolysaccharide (LPS) or pro-inflammatory cytokines. Following culture, cell viability and tissue histomorphometry were assessed with quantification of matrix proteins, resident osteoclasts, ligament cells, monocytes, macrophages, and neutrophils. In the absence of inflammatory factors, culture viability, osteoclasts, and matrix components were maintained. LPS or TNFα stimulation demonstrated an increase in cellular proliferation, monocyte cells, osteoclast differentiation, and matrix degradation. Pathophysiological bone metabolism can be induced via exposure to LPS and direct influence of TNFα within the model despite the absence of systemic circulation, providing a model for inflammatory bone destruction and investigation of the effects of novel therapeutics.
authors.affiliation: Mineralised Tissue Group, Tissue Engineering and Reparative Dentistry, School of Dentistry, Cardiff University, UK. sloanaj@cardiff.ac.uk
authors.forename: A J
authors.initials: AJ
authors.lastname: Sloan
authors.forename: S Y
authors.initials: SY
authors.lastname: Taylor
authors.forename: E L
authors.initials: EL
authors.lastname: Smith
authors.forename: J L
authors.initials: JL
authors.lastname: Roberts
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: X Q
authors.initials: XQ
authors.lastname: Wei
authors.forename: R J
authors.initials: RJ
authors.lastname: Waddington
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D016301:Alveolar Bone Loss / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D024042:Collagen Type I / Q000032:analysis; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000032:analysis; D018836:Inflammation Mediators / Q000276:immunology; D058574:Integrin-Binding Sialoprotein / Q000032:analysis; D053759:Interleukin-23 / Q000032:analysis; D015850:Interleukin-6 / Q000276:immunology; D007527:Isoenzymes / Q000032:analysis; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008336:Mandibular Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D009924:Organ Culture Techniques; D015675:Osteocalcin; D010010:Osteoclasts / Q000473:pathology; D053495:Osteopontin; D010513:Periodontal Ligament / Q000473:pathology; D010518:Periodontitis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000276:immunology; D000071681:Tartrate-Resistant Acid Phosphatase; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; C546872:Ibsp protein, mouse; D018836:Inflammation Mediators; D058574:Integrin-Binding Sialoprotein; D053759:Interleukin-23; D015850:Interleukin-6; D007527:Isoenzymes; D008070:Lipopolysaccharides; C506896:Spp1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D053495:Osteopontin; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: LPS; RANKL/MCSF; bone; inflammation; osteoclast; periodontal disease