Increased Nucleic Acid Receptor Expression in Chronic Periodontitis

Sahingur, Sinem E.; Xia, Xia Juan; Voth, Stephanie; Yeudall, W. Andrew; Gunsolley, John C.

doi:10.1902/jop.2013.120739

Cited by 28 publications

(47 citation statements)

References 35 publications

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“…Although it is beyond the scope of this article, we can speculate that P. gingivalis DNA can be engaged by other nucleic acid sensors as well. In fact, our previous clinical studies also showed increased DAI expression in chronic periodontitis lesions compared to its expression in healthy tissues (14). Future studies are warranted to delineate the extent of involvement of other microbial DNA sensors in periodontitis pathogenesis.…”

Section: Discussionmentioning

confidence: 79%

“…Despite having been fairly well studied in relation to various diseases of infectious or immunological origin, the role of nucleic acid sensing by intracellular PRRs in the pathogenesis of periodontitis has received little attention. Previous clinical studies from our group and others have demonstrated increased TLR9 gene and protein expression in gingival tissues associated with chronic periodontitis (14)(15)(16). TLR9 showed the highest gene expression among all innate receptors, and the increased expression was predominantly localized in the connective tissue and basal epithelial layers (14).…”

mentioning

confidence: 61%

“…Previous clinical studies from our group and others have demonstrated increased TLR9 gene and protein expression in gingival tissues associated with chronic periodontitis (14)(15)(16). TLR9 showed the highest gene expression among all innate receptors, and the increased expression was predominantly localized in the connective tissue and basal epithelial layers (14). It is also well established that the host genetic background affects susceptibility to periodontitis (17).…”

mentioning

confidence: 64%

“…The gingival tissues were harvested from around the maxillary molars at the time of euthanasia, and total RNA was isolated and cDNA was generated as described previously (14). The levels of IL-6, tumor necrosis factor (TNF), and receptor-activator of NF-B ligand (RANKL) expression in gingival tissues of the mice in each group were determined by real-time PCR (Applied Biosystems 7500) using SYBR green master mix (SaBiosciences) and the following specific primer sets: for RANKL, forward, 5= CAG CAT CGC TCT GTT CCT GTA 3=, and reverse, 5= CTG CGT TTT CAT GGA GTC TCA 3=; for IL-6, forward, 5= TCT ATA CCA CTT CAC AAG TCG GA 3=, and reverse, 5= GAA TTG CCA TTG CAC AAC TCT TT 3=; for TNF, forward, 5= CTG AAC TTC GGG GTG ATC GG 3=, and reverse, 5= GGCTTG TCA CTC GAA TTT TGA GA 3=; and for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), forward, 5= AGG TCG GTG TGA ACG GAT TTG 3=, and reverse, 5= GGG GTC GTT GAT GGC AAC A 3=.…”

Section: Methodsmentioning

confidence: 99%

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Toll-Like Receptor 9-Mediated Inflammation Triggers Alveolar Bone Loss in Experimental Murine Periodontitis

et al. 2015

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Chronic periodontitis is a local inflammatory disease induced by a dysbiotic microbiota and leading to destruction of the toothsupporting structures. Microbial nucleic acids are abundantly present in the periodontium, derived through release after phagocytic uptake of microbes and/or from biofilm-associated extracellular DNA. Binding of microbial DNA to its cognate receptors, such as Toll-like receptor 9 (TLR9), can trigger inflammation. In this study, we utilized TLR9 knockout (TLR9 ؊/؊ ) mice and wild-type (WT) controls in a murine model of Porphyromonas gingivalis-induced periodontitis and report the first in vivo evidence that TLR9 signaling mediates the induction of periodontal bone loss. P. gingivalis-infected WT mice exhibited significantly increased bone loss compared to that in sham-infected WT mice or P. gingivalis-infected TLR9 ؊/؊ mice, which were resistant to bone loss. Consistent with this, the expression levels of interleukin 6 (IL-6), tumor necrosis factor (TNF), and receptoractivator of nuclear factor kappa B ligand (RANKL) were significantly elevated in the gingival tissues of the infected WT mice but not in infected TLR9؊/؊ mice compared to their levels in controls. Ex vivo studies using splenocytes and bone marrow-derived macrophages revealed significantly diminished cytokine production in TLR9؊/؊ cells relative to the cytokine production in WT cells in response to P. gingivalis, thereby implicating TLR9 in inflammatory responses to this organism. Intriguingly, compared to the cytokine production in WT cells, TLR9؊/؊ cells exhibited significantly decreased proinflammatory cytokine production upon challenge with lipopolysaccharide (LPS) (TLR4 agonist) or Pam3Cys (TLR2 agonist), suggesting possible cross talk between TLR9, TLR4, and TLR2. Collectively, our results provide the first proof-of-concept evidence implicating TLR9-triggered inflammation in periodontal disease pathogenesis, thereby identifying a new potential therapeutic target to control periodontal inflammation.

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Section: Discussionmentioning

confidence: 79%

mentioning

confidence: 61%

mentioning

confidence: 64%

Section: Methodsmentioning

confidence: 99%

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Toll-Like Receptor 9-Mediated Inflammation Triggers Alveolar Bone Loss in Experimental Murine Periodontitis

et al. 2015

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“…The mRNA levels of TLR2 and TLR9, but not TLR4, were positively correlated with the number of P. gingivalisin subgingival plaque. This study suggests that P. gingivalisinfection induces TLR2 and TLR9 upregulation in patients with periodontitis [33].Moreover,statistically significant upregulation of TLR9 and TLR8 have been reported in chronic periodontitis tissues compared to healthy sites [34]. In another study, gingival tissue samples were obtained from eight chronic periodontitis and nine gingivitis (3 mild; 3 moderate; 3 severe) patients.…”

Section: How Chronic Periodontitis Affects Tlr Activities?mentioning

confidence: 65%

The Role of TLRs in the Pathogenesis of Periodontal Diseases

Gümüş¹

2016

J. Dent. Sci. Ther

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Periodontitis is a complex and multi-factorial inflammatory disease. Dysbiotic microbial communities of keystone pathogens induce host response, which are also responsible for tissuedestructive inflammation and inflammatory bone loss. Microbiata in the microbial dental biofilm stimulate innate immunity via the Toll-like receptor (TLR) family of pattern-recognition receptors. TLRs recognize the antigens and activate pro-inflammatory cytokines in the periodontal tissues. The transition from gingivitis to periodontitis requires both a dysbioticmicrobiota and a susceptible host. Understanding the role of TLRs signaling in the periodontal health and disease may be helpful for providing new insight to the pathogenesis of periodontitis and developing new therapeutic approaches.

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Controlling Alveolar Bone Loss by Hydrogel‐Based Mitigation of Oral Dysbiosis and Bacteria‐Triggered Proinflammatory Immune Response

Chen,

Huang,

Guo

et al. 2024

Adv Funct Materials

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Periodontitis is a chronic infection where abnormal host‐microbiota interactions alter the oral microbiome, trigger a proinflammatory immune response, and cause inflammatory alveolar bone loss. While antibiotics are occasionally necessary for treating periodontitis, their use must be carefully managed to prevent the development of drug resistance and oral dysbiosis. Therefore, it's crucial to develop new treatment strategies for periodontitis that reduce antibiotic dependence while effectively controlling the inflammation triggered by bacteria. In this study, a hydrogel is engineered by grafting cationic polyamidoamine dendrimers (PAMAM‐G3) onto the oxidized carboxymethyl cellulose (OCMC) backbone, resulting in an injectable cationic hydrogel (OCMC‐PAMAM‐G3, O‐P). This hydrogel can capture anionic microbial‐associated molecular patterns (MAMPs), such as lipopolysaccharides (LPS) and cell‐free DNA (cfDNA). These findings reveal that using O‐P application circumvents the disruption of the oral mucosa microbiome caused by traditional antibiotics. Additionally, this hydrogel can mitigate inflammatory alveolar bone loss in a ligature‐induced periodontitis mouse model by alleviating the LPS/cfDNA‐TLR4/9 pathway. Moreover, topical administration of O‐P hydrogel has no significant adverse effects on the oral mucosa microbiome while improving the local subgingival microbiome. The study highlights a strategy targeting MAMPs while avoiding antibiotics, as it can mitigate the bacteria‐triggered proinflammatory immune response and potentially preserve oral dysbiosis.

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Increased Nucleic Acid Receptor Expression in Chronic Periodontitis

Abstract: This study highlights a possible role for nucleic acid receptors in periodontal inflammation. Future investigations will determine whether cytoplasmic receptors and their ligands can be targeted to improve clinical outcomes in periodontitis.

Cited by 28 publications

References 35 publications

Toll-Like Receptor 9-Mediated Inflammation Triggers Alveolar Bone Loss in Experimental Murine Periodontitis

Toll-Like Receptor 9-Mediated Inflammation Triggers Alveolar Bone Loss in Experimental Murine Periodontitis

The Role of TLRs in the Pathogenesis of Periodontal Diseases

Controlling Alveolar Bone Loss by Hydrogel‐Based Mitigation of Oral Dysbiosis and Bacteria‐Triggered Proinflammatory Immune Response

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