The role of lipopolysaccharide in infectious bone resorption of periapical lesion.
BACKGROUND
The role of lipopolysaccharide (LPS) in periapical lesion-induced bone resorption was investigated. Polymyxin B (PMB), a specific inhibitor of LPS, was evaluated to treat the apical lesion.


METHODS
Lipopolysaccharide isolated from two common endodontic pathogens, Fusobacterium nucleatum and Porphyromonas endodontalis, stimulated mouse macrophage (J774) to release interleukin-1alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) in a time-dependent manner.


RESULTS
Combination of LPS further enhanced the stimulation. PMB inhibited these effects significantly. LPS also stimulated matrix metalloproteinase-1 (MMP-1) gene expression in J774, whereas anti-IL-1 alpha and anti-TNF-alpha antibodies, as well as PMB, diminished this effect. A disease model of periapical lesion was established in Wistar rat. Administration of PMB reduced the extent of lesion-associated bone resorption by 76% to approximately 80%, and simultaneously reduced the numbers of MMP-1-producing macrophages.


CONCLUSIONS
It is suggested that LPS released from the infected root canal triggers the synthesis of IL-1 alpha and TNF-alpha from macrophages. These pro-inflammatory cytokines up-regulate the production of MMP-1 by macrophages to promote periapical bone resorption.
Hong
Chi-Yuan
CY
School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin
Sze-Kwan
SK
Kok
Sang-Heng
SH
Cheng
Shih-Jung
SJ
Lee
Ming-Shu
MS
Wang
Tong-Mei
TM
Chen
Chuan-Shuo
CS
Lin
Li-Deh
LD
Wang
Juo-Song
JS
D016301:Alveolar Bone Loss / Q000188:drug therapy / Q000382:microbiology*; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016967:Fusobacterium nucleatum / Q000472:pathogenicity; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism; D010485:Periapical Periodontitis / Q000188:drug therapy / Q000382:microbiology*; D011112:Polymyxin B / Q000494:pharmacology* / Q000627:therapeutic use; D045202:Porphyromonas endodontalis / Q000472:pathogenicity; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D007375:Interleukin-1; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D020781:Matrix Metalloproteinase 1; D011112:Polymyxin B