OC-STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up-regulation of permissive fusogen CD9.

Cell fusion-mediated formation of multinuclear osteoclasts (OCs) plays a key role in bone resorption. It is reported that 2 unique OC-specific fusogens [ i.e.

B10 Cells Alleviate Periodontal Bone Loss in Experimental Periodontitis.

B10 cells can regulate inflammatory responses in innate immunity. Toll-like receptors (TLRs) play an important role in B cell-mediated immune responses in periodontal disease. This study aimed to determine the effects of TLR-activated B10 cells on periodontal bone loss in experimental periodontitis.

Phosphoglycerol dihydroceramide, a distinctive ceramide produced by Porphyromonas gingivalis, promotes RANKL-induced osteoclastogenesis by acting on non-muscle myosin II-A (Myh9), an osteoclast cell fusion regulatory factor.

Among several virulence factors produced by the periodontal pathogen Porphyromonas gingivalis (Pg), a recently identified novel class of dihydroceramide lipids that contains a long acyl-chain has the potential to play a pathogenic role in periodontitis because of its higher level of tissue penetration compared to other lipid classes produced by Pg. However, the possible impact of Pg ceramides on osteoclastogenesis is largely unknown. In the present study, we report that the phosphoglycerol dihydroceramide (PGDHC) isolated from Pg enhanced osteoclastogenesis in vitro and in vivo.

suppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer's disease.

, a keystone pathogen in chronic periodontitis, has been found to associate with remote body organ inflammatory pathologies, including atherosclerosis and Alzheimer's disease (AD). Although has a plethora of virulence factors, much of its pathogenicity is surprisingly related to the overall immunosuppression of the host. This review focuses on aiding suppression of the host's adaptive immune system involving manipulation of cellular immunological responses, specifically T cells and B cells in periodontitis and related conditions.

Soluble RANKL Cleaved from Activated Lymphocytes by TNF-α-Converting Enzyme Contributes to Osteoclastogenesis in Periodontitis.

Host immune responses play a key role in promoting bone resorption in periodontitis via receptor activator of NF-κB ligand (RANKL)-dependent osteoclastogenesis. Both membrane-bound RANKL (mRANKL) expressed on lymphocytes and soluble RANKL (sRANKL) are found in periodontal lesions. However, the underlying mechanism and cellular source of sRANKL release and its biological role in periodontitis are unclear.

Lipopolysaccharides-Induced Suppression of Innate-Like B Cell Apoptosis Is Enhanced by CpG Oligodeoxynucleotide and Requires Toll-Like Receptors 2 and 4.

Innate-like B lymphocytes play an important role in innate immunity in periodontal disease through Toll-like receptor (TLR) signaling. However, it is unknown how innate-like B cell apoptosis is affected by the periodontal infection-associated innate signals. This study is to determine the effects of two major TLR ligands, lipopolysaccharide (LPS) and CpG-oligodeoxynucleotides (CpG-ODN), on innate-like B cell apoptosis.

Local Induction of B Cell Interleukin-10 Competency Alleviates Inflammation and Bone Loss in Ligature-Induced Experimental Periodontitis in Mice.

Interleukin-10 (IL-10)-producing B cells (B10 cells) play a critical role in the immune system balance by negatively regulating inflammatory responses. This study was conducted to determine the effect of local B10 cell induction on periodontal inflammation and bone loss in ligature-induced experimental periodontitis in vivo Purified spleen B cells from C57BL/6J mice (8 to 10 weeks old) were cultured with CD40 ligand (CD40L) and the Toll-like receptor 9 (TLR9) agonist cytidine-phosphate-guanosine oligodeoxynucleotide (CpG) to determine effective IL-10 induction in vitro Silk ligatures (size 7-0) were tied around the mouse maxillary second molars on day 0, followed by the injection of CD40L and CpG into the palatal gingiva on days 3, 6, and 9. All the mice were sacrificed, and samples were collected on day 14.

A novel method of sampling gingival crevicular fluid from a mouse model of periodontitis.

Using a mouse model of silk ligature-induced periodontal disease (PD), we report a novel method of sampling mouse gingival crevicular fluid (GCF) to evaluate the time-dependent secretion patterns of bone resorption-related cytokines. GCF is a serum transudate containing host-derived biomarkers which can represent cellular response in the periodontium. As such, human clinical evaluations of PD status rely on sampling this critical secretion.

A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma.

Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts anti-tumor and anti-osteoclastogenic effects. Although transcriptional and post-transcriptional regulation of IFN-γ is well understood, subsequent modifications of secreted IFN-γ are not fully elucidated. Previous research indicates that some cancer cells escape immune surveillance and metastasize into bone tissue by inducing osteoclastic bone resorption.

Porphyromonas gingivalis exacerbates ligature-induced, RANKL-dependent alveolar bone resorption via differential regulation of Toll-like receptor 2 (TLR2) and TLR4.

Toll-like receptors (TLRs) play a key role in the innate immune responses to periodontal pathogens in periodontal disease. The present study was performed to determine the roles of TLR2 and TLR4 signaling in alveolar bone resorption, using a Porphyromonas gingivalis-associated ligature-induced periodontitis model in mice. Wild-type (WT), Tlr2(-/-), and Tlr4(-/-) mice (8 to 10 weeks old) in the C57/BL6 background were used.

Activation of Toll‐like receptor 9 inhibits lipopolysaccharide‐induced receptor activator of nuclear factor kappa‐ B ligand expression in rat B lymphocytes.

B lymphocytes express multiple TLRs that regulate their cytokine production.We investigated the effect of TLR4 and TLR9 activation on receptor activator of NF‐kB ligand (RANKL) expression by rat spleen B cells. Splenocytes or purified spleen B cells from Rowett rats were cultured with TLR4 ligand Escherichia coli LPS and/or TLR9 ligand CpG‐oligodeoxynucleotide (CpG‐ODN) for 2 days.

DNA-based adaptive immunity protect host from infection-associated periodontal bone resorption via recognition of Porphyromonas gingivalis virulence component.

Background: Porphyromonas gingivalis (Pg) is one of a constellation of oral organisms associated with human chronic periodontitis. While adaptive immunity to periodontal pathogen proteins has been investigated and is an important component of periodontal bone resorption, the effect of periodontal pathogen DNA in eliciting systemic and mucosal antibody and modulating immune responses has not been investigated.

Methods: Rowett rats were locally injected with whole genomic Pg DNA in alum.

Porphyromonas gingivalis infection-associated periodontal bone resorption is dependent on receptor activator of NF-κB ligand.

Porphyromonas gingivalis is one of the oral microorganisms associated with human chronic periodontitis. The purpose of this study is to determine the role of the receptor activator of nuclear factor-κB ligand (RANKL) in P. gingivalis infection-associated periodontal bone resorption.

Selective serotonin reuptake inhibitors attenuate the antigen presentation from dendritic cells to effector T lymphocytes.

Fluoxetine, one of the selective serotonin reuptake inhibitors (SSRIs), has been found to possess immune modulation effects, in addition to its antidepressant effects. However, it remains unclear whether SSRIs can suppress the antigen-presenting function of dendritic cells (DCs). Therefore, Fluoxetine was applied to a co-culture of Aggregatibacter actinomycetemcomitans (Aa)-reactive T cells (×Aa-T) isolated from Aa-immunized mice and DCs.

Aggregatibacter actinomycetemcomitans Omp29 is associated with bacterial entry to gingival epithelial cells by F-actin rearrangement.

The onset and progressive pathogenesis of periodontal disease is thought to be initiated by the entry of Aggregatibacter actinomycetemcomitans (Aa) into periodontal tissue, especially gingival epithelium. Nonetheless, the mechanism underlying such bacterial entry remains to be clarified. Therefore, this study aimed to investigate the possible role of Aa outer membrane protein 29 kD (Omp29), a homologue of E.

Inhibition of matrix metalloproteinase-9 activity by doxycycline ameliorates RANK ligand-induced osteoclast differentiation in vitro and in vivo.

Tetracycline antibiotics, including doxycycli\e (DOX), have been used to treat bone resorptive diseases, partially because of their activity to suppress osteoclastogenesis induced by receptor activator of nuclear factor kappa B ligand (RANKL). However, their precise inhibitory mechanism remains unclear. Therefore, the present study examined the effect of Dox on osteoclastogenesis signaling induced by RANKL, both in vitro and in vivo.

Antibody to receptor activator of NF-κB ligand ameliorates T cell-mediated periodontal bone resorption.

Activated T and B lymphocytes in periodontal disease lesions express receptor activator of NF-κB ligand (RANKL), which induces osteoclastic bone resorption. The objective of this study was to evaluate the effects of anti-RANKL antibody on periodontal bone resorption in vitro and in vivo. Aggregatibacter actinomycetemcomitans outer membrane protein 29 (Omp29) and A.

[In vitro study on the amelioration of T cell-mediated osteoclastogenesis by anti-RANKL-polyclonal antibody].

Purpose: To characterize the effect of receptor activator of NF-kB ligand (RANKL) polyclonal antibody on T cell-mediated osteoclasogenesis.

Methods: Rabbit anti-rat RANKL polyclonal IgG antibody was performed, performing recombinated mouse RANKL-induced osteoclastogenesis in different antibody doses (1microg/mL,5microg/mL and 10microg/mL), the number of TRAP positive multinuclear cells (cells/well) was calculated under microscopy. The cervical lymph nodes in rats were enriched T-cells for in vitro experiments.

Role of periodontal pathogenic bacteria in RANKL-mediated bone destruction in periodontal disease.

Accumulated lines of evidence suggest that hyperimmune responses to periodontal bacteria result in the destruction of periodontal connective tissue and alveolar bone. The etiological roles of periodontal bacteria in the onset and progression of periodontal disease (PD) are well documented. However, the mechanism underlying the engagement of periodontal bacteria in RANKL-mediated alveolar bone resorption remains unclear.

[The effect of B lymphocytes on immune response of periodontal bacteria and osteoclast differentiated reactor-RANKL expression].

Purpose: To study whether B lymphocytes involve in bone resorption in periodontal disease by evaluating RANKL expression of B lymphocytes in immune response to aggregatibacter actinomycetemcomitans (Aa).

Methods: The expression of mRNA transcripts involved in day 1 and day 7 responses of cytokines in cultured rat splenocytes was determined by RT-PCR; The percentage of RANKL-expressing IgG positive cells by B cells in cultured rat splenocytes was measured by flow cytometry; and B lymphocytes capacity for induction of osteoclast differentiation was evaluated by TRAP staining. SPSS 10.

The influence of mineral trioxide aggregate on adaptive immune responses to endodontic pathogens in mice.

This study assessed the influence of mineral trioxide aggregate (MTA) on adaptive immune responses. BALB/c mice were immunized with heat-killed Fusobacterium nucleatum (Fn) in MTA or other control adjuvants, and serum IgG responses to Fn were measured. Either Fn- or Peptostreptococcus anaerobius (Pa)-reactive memory T cells (Tm) were preincubated in vitro with/without MTA and restimulated with Fn or Pa.

Susceptibility of periodontopathogenic and cariogenic bacteria to defensins and potential therapeutic use of defensins in oral diseases.

Antimicrobial peptides play an important role in the human innate immune defense system. In the oral cavity, a number of antimicrobial peptides, including defensins and LL37, are produced from various tissues such as salivary glands, gingival epithelium, tongue and buccal mucosa. These peptides are believed to function as a host defense system by controlling the activities of commensal bacteria and thus preventing the colonization and growth of pathogenic bacteria in oral cavity.

Periodontal bacterial DNA suppresses the immune response to mutans streptococcal glucosyltransferase.

Certain CpG motifs found in bacterial DNA enhance immune responses through Toll-like receptor 9 (TLR-9) and may also demonstrate adjuvant properties. Our objective was to determine if DNA from bacteria associated with periodontal disease could affect the immune response to other bacterial antigens in the oral cavity. Streptococcus sobrinus glucosyltransferase (GTF), an enzyme involved in dental caries pathogenesis, was used as a test antigen.

The new concept of periodontal disease pathogenesis requires new and novel therapeutic strategies.

In this issue Bostanci et al. (2007) demonstrate that receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) were oppositely regulated in gingival crevice fluid (GCF) from periodontitis patients. RANKL, RANK and OPG are key molecules that regulate osteoclast recruitment, differentiation and activation.