TY - JOUR

T1 - A novel ex vivo culture model for inflammatory bone destruction

AU - Sloan, A J

AU - Taylor, S Y

AU - Smith, E L

AU - Roberts, Jessica

AU - Chen, L

AU - Wei, X Q

AU - Waddington, R J

PY - 2013/8

Y1 - 2013/8

N2 - 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.

AB - 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.

KW - Acid Phosphatase

KW - Alveolar Bone Loss

KW - Animals

KW - Cell Differentiation

KW - Cell Proliferation

KW - Cell Survival

KW - Collagen Type I

KW - Disease Models, Animal

KW - Extracellular Matrix Proteins

KW - Inflammation Mediators

KW - Integrin-Binding Sialoprotein

KW - Interleukin-23

KW - Interleukin-6

KW - Isoenzymes

KW - Lipopolysaccharides

KW - Macrophages

KW - Male

KW - Mandibular Diseases

KW - Mice

KW - Monocytes

KW - Neutrophils

KW - Organ Culture Techniques

KW - Osteocalcin

KW - Osteoclasts

KW - Osteopontin

KW - Periodontal Ligament

KW - Periodontitis

KW - Porphyromonas gingivalis

KW - Tumor Necrosis Factor-alpha

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1177/0022034513495240

DO - 10.1177/0022034513495240

M3 - Article

C2 - 23857868

VL - 92

SP - 728

EP - 734

JO - Journal of Dental Research

JF - Journal of Dental Research

SN - 1544-0591

IS - 8

ER -