Cementoblast gene expression is regulated by Porphyromonas gingivalis lipopolysaccharide partially via toll-like receptor-4/MD-2

J Dent Res. 2004 Aug;83(8):602-7. doi: 10.1177/154405910408300804.

Abstract

Lipopolysaccharides are potent inflammatory mediators considered to contribute to destruction of periodontal tissues. Here, we hypothesized that Porphyromonas gingivalis lipopolysaccharide (P-LPS) treatment would regulate gene expression in murine cementoblasts through Toll-like receptor 4. Real-time (RT)-PCR and Northern blot analysis indicated that P-LPS decreased expression of transcripts for osteocalcin (OCN) and receptor activator of nuclear factor kappaB ligand (RANKL). In contrast, a dose-dependent up-regulation in mRNA levels for osteopontin (OPN) and osteoprotegerin (OPG) was observed. Similarly, ELISA demonstrated decreased RANKL and increased OPG levels. A monoclonal antibody specific for mouse TLR-4/MD-2 partially neutralized the P-LPS effect on cementoblasts. These results indicate that exposure of cementoblasts to P-LPS can alter cell function by regulating markers of osteoclastic activity (e.g., RANKL/OPG), thereby potentially affecting the inflammation-associated resorption of mineralized tissues.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Ly / drug effects
  • Antigens, Ly / genetics
  • Antigens, Ly / metabolism*
  • Blotting, Northern
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Dental Cementum / cytology
  • Dental Cementum / drug effects*
  • Dental Cementum / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Lipopolysaccharide Receptors / drug effects
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / metabolism
  • Lipopolysaccharides / pharmacology*
  • Lymphocyte Antigen 96
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Transgenic
  • NF-kappa B / metabolism
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteopontin
  • Osteoprotegerin
  • Porphyromonas gingivalis*
  • RANK Ligand
  • RNA, Messenger / analysis
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Tumor Necrosis Factor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / metabolism
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Up-Regulation / drug effects

Substances

  • Antigens, Ly
  • Carrier Proteins
  • Glycoproteins
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Ly96 protein, mouse
  • Lymphocyte Antigen 96
  • Membrane Glycoproteins
  • NF-kappa B
  • Osteoprotegerin
  • RANK Ligand
  • RNA, Messenger
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • Sialoglycoproteins
  • Spp1 protein, mouse
  • Tnfrsf11a protein, mouse
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Osteocalcin
  • Osteopontin