IL-1-induced receptor activator of NF-κB ligand in human periodontal ligament cells involves ERK-dependent PGE2 production

Fukushima, Hidefumi; Jimi, Eijiro; Okamoto, Fujio; Motokawa, Wataru; Okabe, Koji

doi:10.1016/j.bone.2004.09.011

Cited by 68 publications

(57 citation statements)

References 38 publications

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“…We have previously established in this in vitro experimental model that RANKL up-regulation is partly mediated by PGE 2 , following COX-2 expression [15]. It was recently shown that IL-1β induces RANKL in human periodontal ligament cells, mediated by PGE 2 production, possibly through all three MAPKs [23], although others implicate mainly the ERK (p44/42) MAPK in this PGE 2 -mediated event [24]. In the present study in bone marrow stromal cells, P. gingivalis-induced COX-2 expression was significantly down-regulated with the p38 inhibitor, indicating that the p38 MAPK is implicated in this induction.…”

Section: Discussionmentioning

confidence: 95%

“…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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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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

Reddi

Brown

Belibasakis

2011

Microbial Pathogenesis

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“…Interestingly, these proinflammatory factors have also been found to enhance RANKL expression in PDLCs, OBs, and stromal cells, and to promote pre-OC recruitment. 4,[24][25][26][27][28] Based on these results, we concluded that the mechanism of osteoclastogenesis regulated by hypoxia and compression overlap in the NF-kB pathway (Figure 3). Similar to our previous findings, 5 expression of RANKL in the compressed PDLCs peaked at 6 hours and was significantly higher than that of the PDLCs under hypoxia, while no significant difference was detected between the compressed PDLCs and the control group at 72 hours ( Figure 2A).…”

Section: Discussionmentioning

confidence: 81%

Compression and hypoxia play independent roles while having combinative effects in the osteoclastogenesis induced by periodontal ligament cells

Yang

et al. 2015

The Angle Orthodontist

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Objective: To investigate the isolated and combined effects of compression and hypoxia on the osteoclastogenesis induced by periodontal ligament cells (PDLCs). Materials and Methods: A periodontal ligament tissue model (PDLtm) was established by 3-D culturing human PDLCs on a thin sheet of poly lactic-co-glycolic acid scaffold. The PDLtm was treated with hypoxia and/or compression for 6, 24, or 72 hours. After that, a real-time polymerase chain reaction was used for gene expression analysis. The conditioned media were used for the coculture of osteoblast and osteoclast (OC) precursors; tartrate-resistant acid phosphatase staining was done to examine OC formation. Results: Either compression or hypoxia alone significantly up-regulated the gene expression of pro-osteoclastogenic cytokines in the PDLtm and enhanced osteoclastogenesis in the cocultures, and the combination of the two had significantly stronger effects than either stimulation alone. In addition, comparing the two stimulants, we found that the osteoclastogenic property of the PDLCs peaked earlier (at 6 hours) in the compression group than in the hypoxia group (at 24 hours). Conclusions: Both compressive force and hypoxia may take part in initiating osteoclastogenesis in orthodontic tooth movement and may have combinatory effects, which could update our concepts of the mechanisms involved in the initiation of bone resorption on the pressure side of the tooth in question. (Angle Orthod. 2016;86:66-73.)

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“…Periodontal ligament fibroblasts have been shown to be relevant for bone formation in periodontal regenerative procedures and also to express RANKL in response to different interleukin-1, lipopolysaccharide, prostaglandin E2 and mechanical stress [24][25][26] by the activation of mitogenassociated protein kinases (MAPKs). In osteoblasts exposed to the whole bacteria Porphyromonas gingivalis, RANKL mRNA levels were dependent on activation of activator protein 1 (AP-1); but, surprisingly, this activation did not require p38, ERK MAPKs or the phosphoinositol-3-kinase (PI3K) pathway [27].…”

Section: Discussionmentioning

confidence: 99%

RANKL expression is differentially modulated by TLR2 and TLR4 signaling in fibroblasts and osteoblasts

Leite¹,

Aquino²,

Guimarães³

et al. 2014

Immunol Innov

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IL-1-induced receptor activator of NF-κB ligand in human periodontal ligament cells involves ERK-dependent PGE2 production

Cited by 68 publications

References 38 publications

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

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

Compression and hypoxia play independent roles while having combinative effects in the osteoclastogenesis induced by periodontal ligament cells

RANKL expression is differentially modulated by TLR2 and TLR4 signaling in fibroblasts and osteoblasts

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