The role of interleukin-1beta in Porphyromonas gingivalis lipopolysaccharide-induced bone resorption
Chiang, C.-Y.; Fu, E.; Shen, E.-C.
Zhonghua Yi Xue Za Zhi 65(5): 225-230
2002
ISSN/ISBN: 0578-1337 PMID: 12166767 Document Number: 541960
Pro-Interleukin (IL)-1beta is not fully active after synthesis. It acquires activity after secretion when cleaved with a specific intracellular protease, IL-1beta converting enzyme (ICE). ICE-deficient animals display impaired production of IL-1beta. Upon stimulation with lipopolysaccharide (LPS), ICE homozygous deficiency mutants are highly resistant to endotoxic shock. Lipopolysaccharides have also been identified as major bacterial factors in bone resorption. However, the exact mechanisms by which LPS stimulates bone resorption in ICE-deficient animals are still uncertain. The present study investigated how interleukin-1beta activity mediates LPS-induced bone resorption in vivo. In our dose-dependent experiment, 10 six-week-old ICE-deficient mice were divided into two groups and injected with one of two concentrations of P gingivalis (A7436) LPS: 500 microg and 100 microg. Ten wild-type mice (164BBC) served as the control subjects. Frozen sections of calvaria were stained with tartrate-resistant acid phosphatase (TRAP) for histomorphometric analysis to quantify osteoclast number, area, and activity. Inhibition of 38% in osteoclast index and osteoclast surface was observed in 500 microg LPS-induced ICE-deficient mice compared with the wild-type mice. However, the data were not significantly different between these two groups at 100 microg of LPS injection, but they were still higher than those of control subjects. Bone-resorbing activities of the osteoclast showed no significant differences between ICE-deficient mice and wild-type mice. Within limitations of the study, we suggest that LPS-induced bone resorption may be caused by enhancing osteoclastogenesis, not by increasing osteoclast resorbing activity. The LPS leading bone resorption is, at least, partially mediated by IL-1beta at higher concentrations.