Radiographic and micro-computed tomographic imaging of lipopolysaccharide-mediated bone resorption.
OBJECTIVE
Chronic otitis media and cholesteatomas cause hearing loss as a result of bony erosion. This bone resorption is known to be more aggressive when cholesteatomas become infected. The most common organism isolated from both diseases is the gram-negative bacterium Pseudomonas aeruginosa. Lipopolysaccharide (LPS), a major virulence factor found in the gram-negative bacterial cell wall, is well known to incite inflammatory bone resorption. The mechanisms underlying this process, however, are poorly understood. In this study, we developed a mouse model of calvarial osteolysis in which resorption was reliably imaged by plain radiography and micro-computed tomography (micro-CT).


METHODS
A murine calvarial model was developed to study bone resorption induced by P aeruginosa LPS. Calvariae from wild-type and knockout mice used in this model were imaged by plain radiography and micro-CT.


RESULTS
A high degree of correlation between plain radiography and micro-CT was identified (R2 = 0.8554). Furthermore, maximal LPS-induced bone resorption required functioning toll-like receptor (TLR) 2, TLR4, and myeloid differentiation factor 88 (MyD88).


CONCLUSIONS
We have developed a successful model of inflammatory osteolysis in which plain radiography can reliably delineate induced bone resorption. In vivo, we have shown that P aeruginosa LPS signals via TLR2, as well as TLR4 through MyD88.
Nason
Robert
R
Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Lee
Dong H
DH
Jung
Jae Y
JY
Chole
Richard A
RA
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D010014:Osteolysis / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000503:physiopathology; D010033:Otitis Media / Q000000981:diagnostic imaging*; D011550:Pseudomonas aeruginosa; D051195:Toll-Like Receptor 2 / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology; D014057:Tomography, X-Ray Computed / Q000379:methods
D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4