Antagonists of Wnt/β‐catenin signalling in the periodontitis associated with type 2 diabetes and smoking

Miranda, Tamires Szeremeske; Napimoga, Marcelo Henrique; Feres, Magda; Marins, Letícia Macedo; Cruz, Daniele Ferreira; Silva, Hélio Doyle P. da; Duarte, Poliana Mendes

doi:10.1111/jcpe.12854

Cited by 28 publications

(27 citation statements)

References 44 publications

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“…Results also revealed no expressive correlations for the protein levels of the cytokines studied among the biological matrices. In agreement with this findings, a prior investigation from our group did not report correlation in the protein levels of IL‐1ß, TNF‐α and IL‐6 between serum and periodontal tissues . The disagreement in cytokine concentration between the biological milieus and the lack of meaningful correlations between their protein levels in serum and in tissue/GCF indicates that cytokine abundance might vary according to their immunological activities in distinct locations or situations, as previously suggested in the medical field .…”

Section: Discussionsupporting

confidence: 90%

“…PD (mm), CAL (mm) and BoP (presence/absence) were assessed at six sites per tooth using a manual periodontal probe by a same calibrated examiner (T.S.M), as previously described . Samples were taken within 1 week after clinical examination.…”

Section: Methodsmentioning

confidence: 99%

“…The protein levels of interleukin (IL)‐1β, IL‐6 and tumour necrosis factor (TNF)‐α in the serum, tissue and CGF were analyzed by a multiplex fluorescent bead‐based immunoassay, as previously described . Data were obtained from 25 μL of each sample for each well.…”

Section: Methodsmentioning

confidence: 99%

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Protein and mRNA detection of classic cytokines in corresponding samples of serum, gingival tissue and gingival crevicular fluid from subjects with periodontitis

Duarte

Abreu

Vilela

et al. 2018

J of Periodontal Research

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Background and objective:Little is known about the correspondence of cytokines detected among the different biological matrices used in periodontal research and whether locally-detected cytokine mRNA can also be identified at the translated protein level. The aims of this study were to compare: (a) the detection of classic cytokines at protein level in corresponding samples of serum, gingival tissue and gingival crevicular fluid (GCF) in subjects with periodontitis and (b) the detection of cytokines at protein level in GCF and tissue with their detection at mRNA level in tissue. Material and methods:Protein concentrations of IL-1β, IL-6 and TNFα were measured in corresponding samples of GCF, gingival tissue and serum from 125 subjects with chronic periodontitis by multiplex immunoassay. The mRNA levels of these cytokines were evaluated in the same gingival tissue by qPCR. Results:The mean protein concentrations of IL-1ß and TNFα were higher in tissue and GCF than in serum (P < 0.05). The mean protein concentration of IL-6 was higher in tissue, followed by serum and GCF, respectively (P < 0.05). Using serum as the gold standard, detection of IL-1ß in GCF and IL-6 in tissue had the highest sensitivity (100%), while detection of IL-6 in the GCF had the lowest sensitivity (77.9%). Using tissue as the gold standard, the detection sensitivities of IL-1ß, IL-6 and TNFα were 93.6%, 78.4% and 94.2%, respectively, in GCF. Using mRNA as the gold standard, the detection of IL-1ß and IL-6 at the protein level in tissue (100.0%) had the highest sensitivity, while the detection of IL-6 in GCF (77.9%) had the lowest sensitivity.Conclusion: Tissue and GCF exhibited overall higher protein concentrations of cytokines than serum. GCF presented good reliability for identifying the target cytokines at protein level, when compared with detecting tissue cytokines at protein level. GCF and tissue presented high sensitivities for detecting cytokines at the protein level, when compared with detecting tissue cytokines at the mRNA level. The sensitivity for the identification of cytokines in the GCF depended on the target cytokine, where IL-6 was the least likely cytokine to be detected in this matrix. K E Y W O R D Scytokines, mRNA, protein levels | 175 DUARTE ET Al.

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Section: Discussionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

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Protein and mRNA detection of classic cytokines in corresponding samples of serum, gingival tissue and gingival crevicular fluid from subjects with periodontitis

Duarte

Abreu

Vilela

et al. 2018

J of Periodontal Research

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“…In our current study, periodontitis interference might invoke some signals resulting in decreased osteoclasts in the alveolar bone of the 335‐Tg mice. Since the existing results indicate that miR‐335‐5p can activate the Wnt canonical pathway to promote osteogenesis and inhibit bone loss in periodontitis and the Wnt signaling has been divided as canonical and noncanonical pathway, both of which are pivotal in the periodontal homeostasis, whether miR‐335‐5p can regulate bone metabolism through the noncanonical Wnt pathway has potential deserving further investigation. Consequently, in addition to the inhibitive effects of exosome miR‐335 on osteoclast‐related bone metastasis via repressing RANKL, our study is the first to find that overexpression of miR‐335‐5p in vivo negatively involves in periodontal bone destruction.…”

Section: Discussionmentioning

confidence: 99%

Potential roles of miR‐335‐5p on pathogenesis of experimental periodontitis

Lian

Liu

et al. 2019

J of Periodontal Research

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Background and Objective Periodontitis is a prevalent oral disease responsible for tooth loss. MicroRNAs have been proven crucial in bone disorders over the past decades. Promotive effect on osteogenic activities by microRNA‐335‐5p (miR‐335‐5p) has been well demonstrated, but its role involved in the pathogenesis of periodontitis remains elusive. In this study, we established experimental periodontitis (EP) on transgenic mice overexpressing miR‐335‐5p (335‐Tg) to investigate the novel effects of miR‐335‐5p on periodontal inflammation and bone loss. Methods Experimental periodontitis was established via ligation. The expression of inflammatory and osteoclastic genes was examined by quantitative real‐time PCR (qPCR). Morphology of alveolar bone was analyzed by microcomputed tomography (μCT). Hematoxylin and eosin (H&E), tartrate‐resistant acid phosphatase (TRAP), and Toll‐like receptor 4 (TLR4) immunohistochemistry (IHC) staining were conducted for histological analysis. Results The expression of miR‐335‐5p decreased significantly in the periodontal tissues of EP. Compared to the WT‐EP group, μCT analysis showed less bone loss in the 335‐Tg‐EP group accompanying with a decreased number of TRAP‐positive osteoclasts. H&E and IHC staining exhibited attenuated inflammation and TLR4 expression in the 335‐Tg‐EP group. Furthermore, reduced expressions of IL‐1β, IL‐6, TNF‐α, and TLR4 were also detected in the 335‐Tg‐EP group. Overexpression of miR‐335‐5p in vivo weakened the periodontal bone destruction and inflammation compared with the WT‐EP group. Conclusions Our data exhibit novel roles of miR‐335‐5p in preventing bone loss and inflammation in experimental periodontitis.

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“…Sclerostin, the osteocyte-expressed and secreted inhibitor of bone formation, can also be found at higher levels in the crevicular fluid from periodontitis patients and could be a more reliable measure for diagnosis or prognosis of disease than RANKL [ 41 ]. Also in serum or in gingival biopsies, sclerostin was increased in chronic periodontitis patients [ 42 ]. Higher levels of sclerostin were also reported in the peri-implant crevicular fluid in patients with peri-implantitis [ 43 ].…”

Section: Introductionmentioning

confidence: 99%

The Osteocyte as a Novel Key Player in Understanding Periodontitis Through its Expression of RANKL and Sclerostin: a Review

Vries

Huesa

2019

Curr Osteoporos Rep

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Purpose of Review Periodontitis is the inflammation-associated bone loss disease of the alveolar bone that surrounds teeth. Classically, the emphasis on the etiology of periodontitis has been on the products of periodontal pathogens that lead to an inflammatory response of the soft tissues of the periodontium, eventually leading to activation of osteoclasts that degrade the alveolar bone. Until recently, the response of osteocytes that populate the alveolar bone, and that are known for their regulatory role in bone anabolism and catabolism, has not been addressed. Recent Findings This review demonstrates that osteocytes play a key contributing role in periodontitis progression in various experimental mouse and rat periodontitis models. Osteocytes are the key expressing cells of both osteoclast differentiation factor RANKL as well as osteoblast activity regulator sclerostin. Targeted deletion of RANKL in osteocytes prevents osteoclast formation, thereby impairing periodontitis, despite the pressure of periodontitis-associated bacteria. Antibodies against the osteocyte-derived protein sclerostin inhibit and partially revert periodontitis by stimulating bone formation. Summary Experimental mouse and rat periodontitis models strongly indicate a key role for the bone-encapsulated osteocyte in understanding periodontitis etiology.

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Antagonists of Wnt/β‐catenin signalling in the periodontitis associated with type 2 diabetes and smoking

Abstract: SOST and DKK1 were upregulated in patients with CP presenting DM and/or smoking. DM, alone or with smoking, particularly influenced the correlations of SOST and DKK1 with each other and with the other biomarkers mostly at mRNA levels, as well as with periodontal pathogens.

Cited by 28 publications

References 44 publications

Protein and mRNA detection of classic cytokines in corresponding samples of serum, gingival tissue and gingival crevicular fluid from subjects with periodontitis

Protein and mRNA detection of classic cytokines in corresponding samples of serum, gingival tissue and gingival crevicular fluid from subjects with periodontitis

Potential roles of miR‐335‐5p on pathogenesis of experimental periodontitis

The Osteocyte as a Novel Key Player in Understanding Periodontitis Through its Expression of RANKL and Sclerostin: a Review

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