We previously demonstrated that interleukin-1 (IL-1) and tumor necrosis factor (TNF) activities only partially account for calvarial bone resorption induced by local application of lipopolysaccharide (LPS) in mice. The present study was undertaken to determine the role and relative contribution of IL-11 and prostaglandin(s) (PG[s]) in LPS-induced bone resorption in vivo. A one-time dose of LPS was injected into the subcutaneous tissue overlying calvaria of mice lacking IL-1 receptor type I (IL-1RI ؊/؊ ), mice lacking TNF receptor p55 and IL-1RI (TNFRp55 ؊/؊ -IL-1RI ؊/؊ ), and wild-type mice. Mice were then treated with injections of anti-IL-11 monoclonal antibody (MAb), indomethacin, or phosphate-buffered saline (PBS) and sacrificed 5 days later. Histological sections stained for tartrate-resistant acid phosphatase (TRAP) were quantified by histomorphometric analysis. At low doses of LPS (100 g/mouse), the percentages of bone surface covered by osteoclasts were found to be similar in three strains of mice. The increase was reduced by 37% with anti-IL-11 MAb and by 46% with indomethacin. At higher doses of LPS (500 g/mouse), we found an eightfold increase in these percentages in wild-type mice and a fivefold increase in these percentages in IL-1RI؊/؊ and TNFRp55 ؊/؊ ؊IL-1RI ؊/؊ mice after normalizing with the value from the saline-PBS control group in the same strain of mice. The increase was reduced by 55 and 69% in wild-type mice and by 50 and 57% in IL-1RI؊/؊ and TNFRp55 ؊/؊ ؊IL-1RI ؊/؊ mice treated with anti-IL-11 MAb or indomethacin, respectively. Our findings suggest that in vivo, at low doses of LPS (100 g/mouse), LPS-induced bone resorption is mediated by IL-11 and PGs, while at high doses of LPS (500 g/mouse), it is mediated by IL-11, PGs, IL-1, and TNF signaling.
IL-11 and PGs mediate LPS-induced bone resorption by enhancing osteoclastogenesis independently of the IL-1 or TNF signaling.Bone resorption is a feature of chronic inflammatory diseases such as rheumatoid arthritis, osteomyelitis, bacterial arthritis, and periodontitis (16). Periodontitis is a common inflammatory disorder that often leads to irreversible alveolar bone resorption and tooth loss among adults and is characterized as a peripheral infection involving species of gram-negative organisms (37). The key issue to be addressed in these diseases is how bacteria cause pathological bone loss. Lipopolysaccharide (LPS), a component of the outer membranes of all gram-negative bacteria (28), was the first bacterial component shown to be capable of inducing bone resorption in vitro (16). Although LPS has been identified as a major bacterial bone-resorbing factor, the cellular mechanism by which LPS stimulates bone resorption has not been fully elucidated. Understanding the means by which LPS enhances bone resorption would provide an effective therapeutic strategy to prevent and treat bacterially induced bone resorption.It is known that LPS triggers the inflammatory process both locally and systemically and stimulates cytokine secretion (16,38). L...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.