osteoprotegerin and Periapical-Diseases

The aim of the present study was to evaluate the effects of calcium hydroxide (Ca[OH]. Within the limitations of the present study, it can be concluded that addition of ibuprofen or ciprofloxacin to Ca(OH)

Topics: Anti-Inflammatory Agents, Non-Steroidal; Calcium Hydroxide; Ciprofloxacin; Humans; Ibuprofen; NF-kappa B; Osteoprotegerin; Periapical Diseases; RANK Ligand

Accumulating evidence indicates that the immune and skeletal systems interact with each other through various regulators during the osteoclastogenic process. Among these regulators, the bioactive lipid sphingosine-1-phosphate (S1P), which is synthesized by sphingosine kinase 1/2 (SPHK1/2), has recently been recognized to play a role in immunity and bone remodeling through its receptor sphingosine-1-phosphate receptor 1 (S1PR1). However, little is known regarding the potential role of S1PR1 signaling in inflammatory bone loss. We observed that SPHK1 and S1PR1 were upregulated in human apical periodontitis, accompanied by macrophage infiltration and enhanced expression of receptor activator of NF-κB ligand (RANKL, an indispensable factor in osteoclastogenesis and bone resorption) and increased numbers of S1PR1-RANKL double-positive cells in lesion tissues. Using an in vitro co-culture model of macrophages and bone marrow stromal cells (BMSCs), it was revealed that in the presence of lipopolysaccharide (LPS) stimulation, macrophages could significantly induce SPHK1 activity, which resulted in activated S1PR1 in BMSCs. The activated S1P-S1PR1 signaling was responsible for the increased RANKL production in BMSCs, as S1PR1-blockage abolished this effect. Applying a potent S1P-S1PR1 signaling modulator, Fingolimod (FTY720), in a Wistar rat apical periodontitis model effectively prevented bone lesions in vivo via downregulation of RANKL production, osteoclastogenesis, and bone resorption. Our data unveiled the regulatory role of SPHK1-S1PR1-RANKL axis in inflammatory bone lesions and proposed a potential therapeutic intervention by targeting this cell-signaling pathway to prevent bone loss. © 2018 American Society for Bone and Mineral Research.

Topics: Adult; Aged; Animals; Autophagy; Biomarkers; Bone Resorption; Cell Communication; Down-Regulation; Female; Humans; Inflammation; Macrophages; Male; Mesenchymal Stem Cells; Mice; Middle Aged; Models, Biological; Osteogenesis; Osteoprotegerin; Periapical Diseases; Phosphotransferases (Alcohol Group Acceptor); RANK Ligand; Rats, Wistar; RAW 264.7 Cells; Receptors, Lysosphingolipid; Signal Transduction; Up-Regulation; Young Adult

Long-term sequential expression of receptor activator of NF-κB ligand (RANKL) and osteoprotegrin (OPG) in lipopolysaccharide (LPS)-induced rat periapical lesions has not been studied..   Seventy-two 4-week-old Wistar rats were divided into eight experimental groups and one control group (eight animals in each).. Lipopolysaccharide-induced periapical lesions were produced in rats by occlusal exposure of the pulp of their lower first molars in all experimental groups but not the control group. The extent of periapical destruction was measured by radiographic imaging. RANKL and OPG mRNA were measured in all tissue sections containing the periapical lesions as well as the control group every week from week 1 to week 8 by real-time quantitative reverse transcription polymerase chain reaction. RANKL and OPG protein were determined by immunohistochemistry. Osteoclasts were identified by enzyme histochemistry.. The sequential changes in the mRNA and protein expression of RANKL and OPG were largely compatible with the occurrence of osteoclasts histologically and enzymes histochemically, as well as the mean areas of the periapical lesions radiographically during long-term observation of the LPS-induced rat periapical lesions.. This study may be the first to demonstrate the long-term RANKL and OPG expression every week from week 1 to week 8 using LPS to produce periapical infection in a Wistar rat model. The long-term findings of high expressions of RANKL and OPG further extend the potential application of the Wistar rat model for future experimental trials using RANKL inhibitor to evaluate the treatment outcome for LPS-induced rat periapical lesions.

Topics: Acid Phosphatase; Alveolar Bone Loss; Animals; Biomarkers; Cell Count; Dental Pulp Exposure; Disease Models, Animal; Escherichia coli; Giant Cells; Image Processing, Computer-Assisted; Immunohistochemistry; Isoenzymes; Lipopolysaccharides; Male; Osteoclasts; Osteoprotegerin; Periapical Diseases; Radiography, Bitewing; RANK Ligand; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase; Time Factors

The aim of this research was to study the effects of estrogen deficiency on the receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) synthesis in the periapical lesions that were induced in ovariectomized (OVX) and sham-ovariectomized (Sham) rats. After mandibles were collected, the enzyme histochemical test for tartrate-resistant acid phosphatase and immunohistochemical examination for RANKL and OPG were performed. On days 0, 7, and 28, the numbers of osteoclasts in the periapical areas of the OVX rats were significantly more than those of the Sham group. The data had statistical differences on days 7, 21, and 28 for RANKL-positive cells between the 2 groups. The number of OPG-positive cells of the OVX rats was more than that of the Sham group at the early stage of estrogen deficiency (day 7). Estrogen deficiency-induced severe periapical bone resorption might be mediated by overexpression of RANKL. At the early stage of estrogen deficiency, the osteoblastogenesis was also accelerated, which was shown as a kind of reactive protective response.

Topics: Animals; Estrogens; Female; Osteoclasts; Osteoprotegerin; Periapical Diseases; RANK Ligand; Rats; Rats, Sprague-Dawley

A connection of herpesvirus periapical infection with symptomatic and large-size periapical lesions has been recognized in adult patients, but no data exist about a possible involvement of herpesviruses in severe periapical pathosis in children. Herpesviruses have the potential to elicit potent bone resorption-inducing cytokines in mammalian cells.. This study aimed to determine the occurrence of human cytomegalovirus and Epstein-Barr virus DNA, and mRNA transcripts of receptor activator of nuclear kappa B ligand (RANKL), osteoprotegerin, core binding factor alpha-1, colony stimulating factor-1, transforming growth factor-beta, and monocyte chemoattractant protein-1 in periapical symptomatic pathosis of deciduous teeth.. Twelve deciduous molar teeth from patients aged 2-8 years were extracted due to severe periapical infection, and granulomatous tissue adherent to the root tip of the extracted teeth was collected using a surgical knife. Non-diseased pulpal tissue, obtained from 12 teeth extracted for orthodontic reasons, served as negative control. Polymerase chain reaction assays were employed to identify herpesvirus DNA and cytokine gene expression, using established polymerase chain reaction primers and procedures.. Seven (58%) of the periapical lesions yielded human cytomegalovirus and eight (67%) Epstein-Barr virus. Only one (8%) periapical lesion showed neither human cytomegalovirus nor Epstein-Barr virus. In healthy pulpal tissue, one (8%) specimen demonstrated human cytomegalovirus and another (8%) specimen revealed Epstein-Barr virus. Of the cytokines examined, RANKL expression showed significantly higher occurrence in periapical pathosis than in healthy pulpal tissue (P < 0.040). No relationship was identified between the type of herpesvirus and cytokine expression in the periapical lesions studied.. The present findings provide evidence of a putative role of human cytomegalovirus and Epstein-Barr virus in the pathogenesis of symptomatic periapical pathosis in deciduous teeth. Increased RANKL expression in periapical lesions may be of pathogenetic significance.

Topics: Bone Resorption; Carrier Proteins; Chemokine CCL2; Child; Child, Preschool; Core Binding Factor Alpha 1 Subunit; Cytokines; Cytomegalovirus; DNA, Viral; Female; Glycoproteins; Herpesvirus 4, Human; Humans; Ligands; Macrophage Colony-Stimulating Factor; Male; Membrane Glycoproteins; Osteoclasts; Osteoprotegerin; Periapical Diseases; Periapical Granuloma; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Tooth, Deciduous; Tumor Necrosis Factor-alpha