<i>Retracted:</i> Role of toll‐like receptor 2 in inflammation and alveolar bone loss in experimental peri‐implantitis versus periodontitis

Yu, Xinbo; Hu, Yang; Freire, Marcelo; Yu, Pei; Kawai, Toshihisa; Han, Xiaozhe

doi:10.1111/jre.12492

Cited by 40 publications

(52 citation statements)

References 40 publications

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“…Total RNA was isolated from cells using RNA-Bee isolation reagent (AMS Biotechnology, Cambridge, MA, USA), following the manufacturer's instructions, and subjected to reverse transcription with the Verso cDNA Synthesis Kit (Thermo Fisher Scientific) in the presence of random primers and oligo-dT. Gene expression was quantified using the LightCycler 480 SYBR Green Mouse model of ligature-induced periodontitis OC-STAMP-KO mice (The Jackson Laboratory) or wild-type (WT) mice (6-8 wk old, C57BL/J male, n = 5-6) were placed with a 5-0 silk ligature (Ethicon, Guaynabo, Puerto Rico, USA) on the upper left second molar, whereas the upper right second molar without ligature was used as a control, following the protocol that was developed by our group (12,(24)(25)(26)(27). Because we used mice raised from different breeding cages, especially those of OC-STAMP-KO strains, to avoid the effect of different oral flora, the male mice used for the experiment were cohoused for a week so that all mice harbored similar oral flora, following the protocol reported by other groups (28,29).…”

Section: Real-time Quantitative Pcrmentioning

confidence: 99%

“…Ligatures were removed, and the maxillae were defleshed using dermestid beetles (30). Alveolar bone resorption was measured as previously described (12,(24)(25)(26)(27)31). Briefly, the distance from the cementoenamel junction (CEJ) to the alveolar crest (AC) on the buccal side of each root was measured with a dissection microscope.…”

Section: Alveolar Bone Resorption Measurementmentioning

confidence: 99%

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

Ishii

Ruiz-Torruella²,

Ikeda³

et al. 2018

FASEB j.

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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., OC-stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP)], and permissive fusogen CD9, are involved in OC fusion. In contrast to DC-STAMP-knockout (KO) mice, which show the osteopetrotic phenotype, OC-STAMP-KO mice show no difference in systemic bone mineral density. Nonetheless, according to the ligature-induced periodontitis model, significantly lower level of bone resorption was found in OC-STAMP-KO mice compared to WT mice. Anti-OC-STAMP-neutralizing mAb down-modulated in vitro: 1) the emergence of large multinuclear tartrate-resistant acid phosphatase-positive cells, 2) pit formation, and 3) mRNA and protein expression of CD9, but not DC-STAMP, in receptor activator of NF-κB ligand (RANKL)-stimulated OC precursor cells (OCps). While anti-DC-STAMP-mAb also down-regulated RANKL-induced osteoclastogenesis in vitro, it had no effect on CD9 expression. In our mouse model, systemic administration of anti-OC-STAMP-mAb suppressed the expression of CD9 mRNA, but not DC-STAMP mRNA, in periodontal tissue, along with diminished alveolar bone loss and reduced emergence of CD9 OCps and tartrate-resistant acid phosphatase-positive multinuclear OCs. The present study demonstrated that OC-STAMP partners CD9 to promote periodontal bone destruction by up-regulation of fusion during osteoclastogenesis, suggesting that anti-OC-STAMP-mAb may lead to the development of a novel therapeutic regimen for periodontitis.-Ishii, T., Ruiz-Torruella, M., Ikeda, A., Shindo, S., Movila, A., Mawardi, H., Albassam, A., Kayal, R. A., Al-Dharrab, A. A., Egashira, K., Wisitrasameewong, W., Yamamoto, K., Mira, A. I., Sueishi, K., Han, X., Taubman, M. A., Miyamoto, T., Kawai, T. OC-STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up-regulation of permissive fusogen CD9.

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Section: Real-time Quantitative Pcrmentioning

confidence: 99%

Section: Alveolar Bone Resorption Measurementmentioning

confidence: 99%

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

Ishii

Ruiz-Torruella²,

Ikeda³

et al. 2018

FASEB j.

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“…However, peri-implantitis has become prevalent accompanying the exponential growth of dental implant procedures [2,3]. Peri-implantitis is indicated by infection of implant surrounding soft tissues and bone loss, resulting in implant failure eventually [4][5][6]. The host immune and inflammatory responses caused by plaques on implant surface are crucial in the pathogenesis of peri-implantitis [2,7,8].…”

Section: Introductionmentioning

confidence: 99%

“…Toll-like receptors (TLR) are a family of wellcharacterized pattern recognition receptors (PRRs) and play an important role in the induction of pro-inflammatory cytokines by recognizing the signature molecules of the host innate immunity [25][26][27]. Our previous studies showed that TLR2 are associated with implant bone loss in a mouse model of peri-implantitis [5] and TLR4 is essential for periodontal bone loss [28,29]. In our previous study, we examined the changes of inflammatory cytokines and bone metabolism cytokines in either TLR2 only KO mice or TLR4 only KO mice [5,29].…”

Section: Introductionmentioning

confidence: 99%

RANKL blockade alleviates peri-implant bone loss and is enhanced by anti-inflammatory microRNA-146a through TLR2/4 signaling

Pan

Hu²,

Wang³

et al. 2020

Int J Implant Dent

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Background: The present study was to determine the effect of local anti-RANKL antibody administration in the presence or absence of microRNA-146a on ligature-induced peri-implant bone resorption, and the potential role of TLR2/4 signaling in such effect.Results: Titanium implants were placed in the left maxilla alveolar bone 6 weeks after extraction of first and second molars in C57/BL6 wild-type (WT) and TLR2 −/− TLR4 −/− (TLR2/4 KO) mice. Silk ligatures were tied around the implants 4 weeks after implantation. Anti-RANKL antibody (500 μg/mL) with or without microRNA 146a (miR-146a) (100 nM) was injected into palatal gingiva around implant on days 3, 6, and 9 during 2 weeks of ligation period. Bone resorption around the implants was assessed by 2D imaging using area measurement and 3D imaging using micro-computed tomography (μCT). Real-time quantitative PCR (RT-qPCR) was used to determine the peri-implant gingival mRNA expression levels of pro-inflammatory cytokines (TNF-α) and osteoclastogenesis-related cytokines (RANKL). In both WT and TLR2/4 KO mice, the bone resorption around implants was significantly increased in the ligation only group when compared to the non-ligation group, but TLR2/4 KO mice showed significantly less bone loss compared to WT mice after ligation. As expected, gingival injection of anti-RANKL antibody significantly reduced bone loss compared with the ligation only group in both WT and TLR2/4 KO mice. Moreover, injection of miR-146a in addition to anti-RANKL antibody significantly enhanced the inhibition of bone loss in WT mice but not in TLR2/4 KO mice. Gingival mRNA expressions of RANKL were significantly reduced by anti-RANKL antibody treatment in both WT and TLR2/4 KO mice but were not affected by the additional miR-146a treatment. Gingival mRNA expression of TNF-α was significantly reduced by miR-146a treatment in WT mice but not in TLR2/4 KO mice. The number of gingival inflammatory cell infiltration and peri-implant TRAP-positive cell formation was significantly reduced by the additional miR-146a treatment in WT mice but not in TLR2/4 KO mice.Conclusions: This study suggests that anti-inflammatory miR-146a enhance anti-RANKL-induced inhibition of periimplant bone resorption through the regulation of TLR2/4 signaling and inhibition of TNF-α expression.

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“…Recent studies showed the involvement of pattern recognition receptors (PRRs), including Toll‐like receptors and C‐type lectin receptors, in the pathogenesis of peri‐implantitis. Compared with WT mice in peri‐implantitis, Toll‐like receptor 2 (TLR2) KO mice revealed significantly decreased bone loss by regulating IL‐1β, TNF‐α, and IL‐10 expression . In peri‐implant mucositis and peri‐implantitis, the recruitment of macrophages and the differentiation of osteoclast in gingival tissues may be partly induced by the enhancing of Toll‐like receptor 4 (TLR4) in gingival epithelial cells with the stimulation of titanium ions .…”

Section: Introductionmentioning

confidence: 99%

Wnt5a is involved in LOX‐1 and TLR4 induced host inflammatory response in peri‐implantitis

Zhang

Liu

et al. 2019

J of Periodontal Research

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Background and objective Peri‐implantitis is a plaque‐associated pathological condition occurring in tissues around dental implants, characterized by inflammation in the peri‐implant mucosa and subsequent progressive loss of supporting bone. Wnt5a is the activating ligand of the non‐canonical Wnt signaling pathways and plays important roles in leukocyte infiltration and cytokine/ chemokine production in inflammatory disorders. Previous studies showed that Wnt5a was significantly up‐regulated in gingival tissues of chronic and aggressive periodontitis. However, the roles and the regulatory mechanisms of Wnt5a in peri‐implantitis are not well known. Methods The expression of Wnt5a in gingival tissues collected from 8 healthy implant patients and 8 peri‐implantitis patients was analyzed by Western blotting and immunofluorescence. Porphyromonas gingivalis infected macrophages isolated from the peripheral blood of healthy volunteers were used as an in vitro cellular model of peri‐implantitis. Using neutralizing antibodies, inhibitors and siRNA, the production and roles of Wnt5a in peri‐implantitis were assessed by immunofluorescence, quantitative polymerase chain reaction (RT‐PCR) and Western blotting. Unpaired two‐tailed Student's t test was used to compare qRT‐PCR and Western blotting results. P ≤ .05 was considered statistically significant. Results Wnt5a was highly expressed in the gingival tissues of peri‐implantitis patients. Compared to controls, Wnt5a increased in P gingivalis infected macrophages. Wnt5a production in response to P gingivalis infection was dependent on LOX‐1 and TLR4. Compared to controls, Wnt5a knockdown impaired IL‐1β, MCP‐1, and MMP2 production induced by P gingivalis infection. Conclusion Our results indicate that Wnt5a is involved in LOX‐1 and TLR4 induced inflammatory signature via inflammatory cytokines production in response to P gingivalis infection. These findings demonstrate that Wnt5a maybe an important component of the host immune response in peri‐implantitis.

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Retracted: Role of toll‐like receptor 2 in inflammation and alveolar bone loss in experimental peri‐implantitis versus periodontitis

Cited by 40 publications

References 40 publications

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

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

RANKL blockade alleviates peri-implant bone loss and is enhanced by anti-inflammatory microRNA-146a through TLR2/4 signaling

Wnt5a is involved in LOX‐1 and TLR4 induced host inflammatory response in peri‐implantitis

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