Radiographic and Micro—Computed Tomographic Imaging of Lipopolysaccharide-Mediated Bone Resorption

Abstract

Objectives:

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.