<i>Porphyromonas gingivalis</i>Induces Receptor Activator of NF-κB Ligand Expression in Osteoblasts through the Activator Protein 1 Pathway

Okahashi, Nobuo; Inaba, Hiroaki; Nakagawa, Ichirô; Yamamura, Taihei; Kuboniwa, Masae; Nakayama, Koji; Hamada, Shigeyuki; Amano, Atsuo

doi:10.1128/iai.72.3.1706-1714.2004

Cited by 86 publications

(93 citation statements)

References 63 publications

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“…The present study demonstrates that P. gingivalis enhances PGE 2 production in Jurkat T-cells as well, concomitantly to RANKL. This corroborates previous studies showing that PGE 2 is a potential mediator of RANKL induction by P. gingivalis [19][20][21], although this remains to be proven in the present experimental system as well.…”

Section: Discussionsupporting

confidence: 93%

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Porphyromonas gingivalis Induces RANKL in T-cells

2010

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Porphyromonas gingivalis is an oral pathogen highly implicated in chronic periodontitis, a disease characterized by inflammatory destruction of the tooth-supporting alveolar bone and eventually, tooth loss. T-cell innate immune responses are actively involved in this pathological process. Receptor activator of NF-kappaB Ligand (RANKL) is a cytokine that stimulates bone resorption, while its soluble decoy receptor osteoprotegerin (OPG) blocks its action. This study aimed to investigate in Jurkat T-cells the effects of P. gingivalis on the RANKL-OPG system and the major inflammatory mediator of bone resorption prostaglandin E(2) (PGE(2)). P. gingivalis caused concentration-dependent up-regulation of RANKL gene expression and protein production, assessed by quantitative PCR and ELISA, respectively. PGE(2) production was also enhanced. However, OPG was not detected. In conclusion, P. gingivalis induces RANKL and PGE(2) in T-cells, potentially favoring bone resorption. These T-cell responses to P. gingivalis may contribute to the pathogenesis of inflammatory alveolar bone destruction occurring in chronic periodontitis. ABSTRACTPorphyromonas gingivalis is an oral pathogen highly implicated in chronic periodontitis, a disease characterised by inflammatory destruction of the toothsupporting alveolar bone, and eventually tooth loss. T-cell innate immune responses are actively involved in this pathological process. Receptor Activator of NF-κB Ligand (RANKL) is a cytokine that stimulates bone resorption, while its soluble decoy receptor osteoprotegerin (OPG) blocks its action. This study aimed to investigate in Jurkat T-cells the effects of P. gingivalis on the RANKL-OPG system and the major inflammatory mediator of bone resorption prostaglandin E 2 (PGE 2 ). P. gingivalis caused concentration-dependent up-regulation of RANKL gene expression and protein production, assessed by quantitative PCR and ELISA, respectively. PGE 2 production was also enhanced. However, OPG was not detected. In conclusion, P. gingivalis induces RANKL and PGE 2 in T-cells, potentially favouring bone resorption. These T-cell responses to P. gingivalis may contribute to the pathogenesis of inflammatory alveolar bone destruction occurring in chronic periodontitis.

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Section: Discussionsupporting

confidence: 93%

“…PGE 2 is considered a potential mediator of P. gingivalis-induced RANKL expression [19][20][21]. It is also well established that P. gingivalis is a potent inducer of T-cell responses [22,23].…”

Section: Introductionmentioning

confidence: 99%

Porphyromonas gingivalis Induces RANKL in T-cells

2010

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“…To understand the pathogenesis of periodontitis, it is important to identify the functional role of signalling pathways that are activated by P. gingivalis, such as Activator Protein (AP)-1, MAPKs and NF-κB in various cell types [13,[28][29][30]. In this study, we used a previously established model in bone marrow stromal cells [15], to investigate the putative involvement of MAPK signalling pathways, including p38, JNK and p44/42, in the regulation of RANKL, OPG and COX-2 expression, in response to P. gingivalis challenge.…”

Section: Discussionmentioning

confidence: 99%

“…P. gingivalis is known to induce RANKL expression in osteoblasts [13], gingival fibroblasts and periodontal ligament cells [14], bone marrow stromal cells [15] and T-cells [16]. OPG is a secreted protein that acts as a decoy receptor for RANKL.…”

Section: Introductionmentioning

confidence: 99%

“…There is evidence that MAPKs are implicated in RANKL, OPG and cyclooxygenase (COX)-2 regulation [23][24][25][26][27], and that MAPK signalling cascades can be activated in response to P. gingivalis infection [13,28]. Although previous works investigated the regulation of MAPKs in response to P. gingivalis, or the effects of P. gingivalis on RANKL, OPG and COX-2 expression, the putative cross-talks of these regulatory pathways are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Porphyromonas gingivalis induces RANKL in bone marrow stromal cells: Involvement of the p38 MAPK

Reddi

Brown

Belibasakis

2011

Microbial Pathogenesis

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Periodontitis is a bacterially-induced oral inflammatory disease that is characterised by tissue degradation and bone loss. Porphyromonas gingivalis is a gram negative bacterial species highly associated with the pathogenesis of chronic periodontitis. Receptor activator of nuclear factor-kB ligand (RANKL) induces bone resorption whilst osteoprotegerin (OPG) is a decoy receptor that blocks this process. Cyclooxygenase-2 (COX-2) is an enzyme responsible for the production of prostaglandin (PGE)(2,) which is a major inflammatory mediator of bone resorption. Mitogen-activated protein kinases (MAPK) are intracellular signalling molecules involved in various cell processes, including inflammation. This study aimed to investigate the effect of P. gingivalis on MAPKs and their involvement in the regulation of RANKL, OPG and COX-2 expression in bone marrow stromal cells. P. gingivalis challenge resulted in the phosphorylation of primarily the p38 MAPK. RANKL and COX-2 mRNA expressions were upregulated, whereas OPG was down-regulated by P. gingivalis. The p38 synthetic inhibitor SB203580 abolished the P. gingivalis-induced RANKL and COX-2 expression, but did not affect OPG. Collectively, these results suggest that the p38 MAPK pathway is involved in the induction of RANKL and COX-2 by P. gingivalis, providing further insights into the pathogenic mechanisms of periodontitis. AbstractPeriodontitis is a bacterially-induced oral inflammatory disease that is characterised by tissue degradation and bone loss. Porphyromonas gingivalis is a gram negative bacterial species highly associated with the pathogenesis of chronic periodontitis. Receptor activator of nuclear factor-kB ligand (RANKL) induces bone resorption whilst osteoprotegerin (OPG) is a decoy receptor that blocks this process. Cyclooxygenase-2 (COX-2) is an enzyme responsible for the production of prostaglandin (PGE) 2, which is a major inflammatory mediator of bone resorption. Mitogen-activated protein kinases (MAPK) are intracellular signalling molecules involved in various cell processes, including inflammation. This study aimed to investigate the effect of P. gingivalis on MAPKs and their involvement in the regulation of RANKL, OPG and COX-2 expression in bone marrow stromal cells. P. gingivalis challenge resulted in the phosphorylation of primarily the p38 MAPK. RANKL and COX-2 mRNA expressions were up-regulated, whereas OPG was down-regulated by P. gingivalis. The p38 synthetic inhibitor SB203580 abolished the P. gingivalis-induced RANKL and COX-2 expression, but did not affect OPG. Collectively, these results suggest that the p38 MAPK pathway is involved in the induction of RANKL and COX-2 by P. gingivalis, providing further insights into the pathogenic mechanisms of periodontitis. KeywordsPorphyromonas gingivalis, Bone marrow stromal cells, Receptor activator of nuclear factor-kB ligand, Osteoprotegerin, Cyclooxygenase -2, p38 MAPK.3

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Porphyromonas gingivalis lipopolysaccharide inhibits the osteoblastic differentiation of preosteoblasts by activating Notch1 signaling

Xing

Fan

et al. 2010

Journal Cellular Physiology

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Although Porphyromonas gingivalis lipopolysaccharide (P-LPS) is known to inhibit osteoblast differentiation, the exact molecular mechanisms underlying this phenomenon remain unclear. Here, we investigated the role of Notch signaling in the osteoblastic differentiation of both MC3T3E-1 cells and primary mouse bone marrow stromal cells (BMSCs). P-LPS stimulation activated the Notch1 signaling cascade and increased expression of the Notch target genes HES1 and HEY1. P-LPS can also act as an inhibitor because it is capable of suppressing Wnt/beta-catenin signaling in preosteoblasts by decreasing both glycogen synthase kinase-3beta (GSK-3beta) phosphorylation and the expression of nuclear beta-catenin. These effects were rescued, however, by inhibiting Notch1 signaling. Furthermore, P-LPS treatment inhibited osteoblast differentiation in preosteoblasts as demonstrated by reductions in alkaline phosphatase activity, osteoblast gene expression, and mineralization, all of which were rescued by suppression of Notch1 signaling. Moreover, inhibition of GSK-3beta, HES1, or HEY1 partially reversed the P-LPS-induced inhibition of osteoblast differentiation. Together, these findings suggest that P-LPS inhibits osteoblast differentiation by promoting the expression of Notch target genes and suppressing canonical Wnt/beta-catenin signaling.

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Porphyromonas gingivalisInduces Receptor Activator of NF-κB Ligand Expression in Osteoblasts through the Activator Protein 1 Pathway

Cited by 86 publications

References 63 publications

Porphyromonas gingivalis Induces RANKL in T-cells

Porphyromonas gingivalis Induces RANKL in T-cells

Porphyromonas gingivalis induces RANKL in bone marrow stromal cells: Involvement of the p38 MAPK

Porphyromonas gingivalis lipopolysaccharide inhibits the osteoblastic differentiation of preosteoblasts by activating Notch1 signaling

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