IL-1B activity partially mediates LPS-induced calvarial bone resorption

PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.Thesis (M.Sc.D.)--Boston University, Henry M. Goldman School of Dental Medicine, 1999.Includes bibliographical references (leaves 41-59).Twenty wild type mice were given a local calvarial injection of 500 [mega]g of E. Coli LPS in 100[mega]l of 9% saline solution and were sacrificed at the following time intervals: day 2, day 5, day 9 and day 14. All the specimens were sectioned, stained, and analysed histomoaphometrically. Osteoclast index and osteoclast surface were the 2 parameters used to assess the amount of bone resorption. Our results show that a single dose of LPS can induce bone resorption by stimulating the production of osteoclasts. The 5 day time point was shown to be the optimum moment at which active murine bone resorption peaks following endotoxin stimulation. To assess the role that IL-1[Beta] plays in LPS induced bone resorption, I.C.E (Interleukin-1[Beta] converting enzyme) mutant mice and their respective wild type were injected with Porphyromonas gingivalis(P.g.) LPS. Two different concentrations of LPS were used: 500[mega]g and 100[mega]g. The mice were sacrificed 5 days following the injection of LPS and the osteoclast response was compared histopathologically between the 4 groups. Our results showed a significant decrease in osteoclast index and osteoclast surface in the IL-1[Beta] deficient mice (ICE (-/-)) compared to the wild type at the 500[mega]g LPS concentration group. (p [less than]0.01). The amount of bone resorption was inhibited by 37%. However, in the 100[mega]g LPS injected group there was no significant difference in bone resorption between ICE (-/-) mice and their wild type littermates. These results suggest that at high concentrations of endotoxin, IL-1[Beta] is a potent in-vivo mediator of the osteolytic properties of LPS. The decrease in bone resorption observed in the mutant mice is associated with a reduction in osteoclastogenesis. At lower doses of endotoxin, IL-1[Beta] activity in LPS induced bone resorption may not be as predominant as that of other mediators