Lipopolysaccharide-Induced Osteoclastogenesis from Mononuclear Precursors: A Mechanism for Osteolysis in Chronic Otitis
AUTOR(ES)
Nason, Robert
FONTE
Springer-Verlag
RESUMO
Osteoclasts are the only cells capable of carrying out bone resorption and therefore are responsible for the osteolysis seen in infectious diseases such as chronic otitis media and infected cholesteatoma. Pseudomonas aeruginosa is the most common organism isolated from these infectious middle ear diseases. In this study, we examined the mechanisms by which P. aeruginosa lipopolysaccharide (LPS) stimulates osteoclastogenesis directly from mononuclear osteoclast precursor cells. Osteoclast precursors demonstrated robust, bone-resorbing osteoclast formation when stimulated by P. aeruginosa LPS only if previously primed with permissive, sub-osteoclastogenic doses of receptor activator of NF-κB ligand (RANKL), suggesting that LPS is osteoclastogenic only during a specific developmental window. Numerous LPS-elicited cytokines were found to be released by osteoclast precursors undergoing P. aeruginosa LPS-mediated osteoclast formation. Two lines of evidence suggest that several cytokines promote Oc formation in an autocrine/paracrine manner. First, inhibition of several cytokine pathways including TNF-α, IL-1, and IL-6 block the osteoclastogenesis induced by LPS. Secondly, increased expression of the receptors for TNF-α and IL-1 was demonstrated by real-time quantitative polymerase chain reaction. Such a mechanism has not previously been established and demonstrates the ability of osteoclast precursors to autonomously facilitate bone destruction.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2674198Documentos Relacionados
- Mechanism of lipopolysaccharide-induced tumor necrosis: requirement for lipopolysaccharide-sensitive lymphoreticular cells.
- Lipoprotein(a) Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Production by Human Mononuclear Cells
- Studies on the mechanism of peptidoglycan- and lipopolysaccharide-induced polyclonal activation.
- Lipopolysaccharide-induced apoptosis in swine lymphocytes in vivo.
- Lipopolysaccharide-Induced Epithelial Monoamine Oxidase Mediates Alveolar Bone Loss in a Rat Chronic Wound Model