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.
Subject(s)
Antigens, Ly/metabolism , Dental Cementum/drug effects , Lipopolysaccharides/pharmacology , Membrane Glycoproteins/metabolism , Porphyromonas gingivalis , Receptors, Cell Surface/metabolism , Animals , Antigens, Ly/drug effects , Antigens, Ly/genetics , Blotting, Northern , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cells, Cultured , Dental Cementum/cytology , 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 , Lymphocyte Antigen 96 , Membrane Glycoproteins/drug effects , Membrane Glycoproteins/genetics , Mice , Mice, Transgenic , NF-kappa B/metabolism , Osteocalcin/genetics , Osteocalcin/metabolism , Osteoclasts/drug effects , Osteoclasts/metabolism , Osteopontin , Osteoprotegerin , RANK Ligand , RNA, Messenger/analysis , Receptor Activator of Nuclear Factor-kappa B , Receptors, Cell Surface/drug effects , Receptors, Cell Surface/genetics , 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 effectsABSTRACT
Parathyroid hormone (PTH) functions as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. In addition to the well-established catabolic effects (activation of bone resorption) of PTH, it is now recognized that intermittent PTH administration has anabolic effects (promotion of bone formation). The aim of this study was to investigate whether intermittent administration of PTH in rodents would block the alveolar bone loss observed in rats when a ligature model of periodontitis is used. Morphometric analysis showed that intermittent PTH administration (40 microg/kg) was able to protect the tooth site from periodontitis-induced bone resorption. In addition, there was a significant reduction in the number of inflammatory cells at the marginal gingival area in sections obtained from animals receiving PTH compared with control animals. These findings demonstrated that intermittent PTH administration was able to protect against periodontitis-associated bone loss in a rodent model.