Regulation of cementoblast function by P. gingivalis lipopolysaccharide via TLR2.
Although cementoblasts express Toll-like receptors (TLR)-2 and -4, little is known regarding the possible participation of cementoblasts in the inflammatory response. We investigated the effects of Porphyromonas gingivalis lipopolysaccharide (LPS), tetra- and penta-acylated lipid A species (designated PgLPS(1435/1449) and PgLPS(1690), respectively), on gene expression of osteoclastogenesis-associated molecules in murine cementoblasts. Real-time quantitative RT-PCR analysis revealed that receptor activator of NF-kappaB ligand (RANKL), interleukin-6, Regulated on activation, normal T-cell expressed, and secreted (RANTES), macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1 were rapidly and dramatically induced upon stimulation with PgLPS(1690), but only slightly induced with PgLPS(1435/1449). Osteoprotegerin, which was expressed constitutively, was not altered significantly. ELISA demonstrated synthesis of corresponding proteins. PgLPS(1690) significantly induced transcripts for NF-kappaB, and this activation was inhibited by pre-treatment with anti-TLR-2 but not with TLR-4 antibodies. These results suggest that cementoblasts participate in the recruitment of osteoclastic precursor cells by up-regulation of chemokines/cytokines.
Nemoto
E
E
Department of Periodontics, School of Dentistry, University of Washington, D322-Health Science Center Box 356365, Seattle, WA 98195-6365, USA.
Darveau
R P
RP
Foster
B L
BL
Nogueira-Filho
G R
GR
Somerman
M J
MJ
D000704:Analysis of Variance; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D018925:Chemokines / Q000096:biosynthesis; D003739:Dental Cementum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression; D006023:Glycoproteins / Q000096:biosynthesis; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D008050:Lipid A / Q000494:pharmacology* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology; D053244:Osteoprotegerin; D016966:Porphyromonas gingivalis / Q000737:chemistry*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D015854:Up-Regulation
D002352:Carrier Proteins; D018925:Chemokines; D006023:Glycoproteins; D018836:Inflammation Mediators; D015850:Interleukin-6; D008050:Lipid A; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D051195:Toll-Like Receptor 2