TY - JOUR
T1 - Lipopolysaccharide-induced osteoclastogenesis from mononuclear precursors
T2 - A mechanism for osteolysis in chronic otitis
AU - Nason, Robert
AU - Jung, Jae Y.
AU - Chole, Richard A.
N1 - Funding Information:
This work was supported by NIH grants R01-DC000263-21 and P30-DC004665-07 to R.A.C. from the National Institute on Deafness and Other Communicative Disorders (National Institutes of Health, Bethesda, MD). R.N. is also supported by NIH training grant T32 DC00022. We would like to thank Mary-Pashia Basse for her technical assistance with real-time PCR experiments.
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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.
KW - Cholesteatoma
KW - Chronic otitis media
KW - Inflammatory osteolysis
KW - RANKL
UR - http://www.scopus.com/inward/record.url?scp=67349254657&partnerID=8YFLogxK
U2 - 10.1007/s10162-008-0153-8
DO - 10.1007/s10162-008-0153-8
M3 - Article
C2 - 19145462
AN - SCOPUS:67349254657
SN - 1525-3961
VL - 10
SP - 151
EP - 160
JO - JARO - Journal of the Association for Research in Otolaryngology
JF - JARO - Journal of the Association for Research in Otolaryngology
IS - 2
ER -