Lack of Toll-like receptor 4 decreases lipopolysaccharide-induced bone resorption in C3H/HeJ mice in vivo.
BACKGROUND
Few in vivo studies have demonstrated whether Toll-like receptor 4 (TLR4) is indispensable for lipopolysaccharide (LPS)-induced bone resorption and little is known about the receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) expression induced by LPS under conditions of lack of TLR4.


METHODS
We compared bone resorption histomorphometrically in C3H/HeN and C3H/HeJ mice that were repeatedly injected with Actinobacillus actionmycetemcomitans LPS into their gingiva every 48 h. RANKL-, interleukin-1beta- and OPG-positive cells in the connective tissue were also compared immunohistochemically.


RESULTS
Bone resorption in C3H/HeJ mice in the fourth, seventh, and tenth injection groups was significantly less than that C3H/HeN mice (P < 0.05). The number of RANKL-positive cells in C3H/HeJ mice in the 10th injection group was significantly smaller than that in C3H/HeN mice (P < 0.05). The numbers of interleukin-1beta-positive cells in C3H/HeJ mice in the seventh and tenth injection groups were significantly decreased compared with those in C3H/HeN mice (P < 0.05). The numbers of OPG-positive cells in C3H/HeN and C3H/HeJ mice gradually increased, but there was no significant difference between the two strains of mice.


CONCLUSIONS
TLR4 is indispensable for LPS-induced bone resorption in vivo.
Nakamura
H
H
Department of Periodontology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Fukusaki
Y
Y
Yoshimura
A
A
Shiraishi
C
C
Kishimoto
M
M
Kaneko
T
T
Hara
Y
Y
D016976:Aggregatibacter actinomycetemcomitans / Q000166:cytology; D016301:Alveolar Bone Loss / Q000209:etiology* / Q000473:pathology; D000818:Animals; D001862:Bone Resorption / Q000209:etiology* / Q000473:pathology; D003239:Connective Tissue Cells / Q000473:pathology; D005881:Gingiva / Q000473:pathology; D007150:Immunohistochemistry; D007267:Injections; D053583:Interleukin-1beta / Q000032:analysis / Q000502:physiology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D053244:Osteoprotegerin / Q000032:analysis / Q000502:physiology; D053245:RANK Ligand / Q000032:analysis / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000502:physiology*
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D053244:Osteoprotegerin; D053245:RANK Ligand; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4