Modulation of Matrix Metalloproteinase 14, Tissue Inhibitor of Metalloproteinase 3, Tissue Inhibitor of Metalloproteinase 4, and Inducible Nitric Oxide Synthase in the Development of Periapical Lesions

Cassanta, Lorena Teodoro de Castro; Rodrigues, Virmondés; Violatti-Filho, Jose Roberto; Neto, Benedito Alves Teixeira; Tavares, Vinícius Marques; Bernal, Eduarda Castelo Branco Araujo; Souza, Danila Malheiros; Araújo, Marcelo Sivieri de; Pereira, Sanívia Aparecida de Lima; Rodrigues, Denise Bertulucci Rocha

doi:10.1016/j.joen.2017.02.020

Cited by 13 publications

(7 citation statements)

References 31 publications

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“…Macrophages can directly interact with the cyst epithelium through the release of certain cytokines, such as TNF-α, that regulate bone growth and resorption. Thus, macrophages could be associated to and explain the immunological theory of RC formation 5,6 .…”

Section: Declaration Of Interestsmentioning

confidence: 98%

Macrophages subpopulations in chronic periapical lesions according to clinical and morphological aspects

et al. 2019

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The aim of this study was to evaluate macrophage M1 and M2 subpopulations in radicular cysts (RCs) and periapical granulomas (PGs) and relate them to clinical and morphological aspects. M1 macrophages were evaluated by the percentage of CD68 immunostaining associated with the inflammatory cytokine TNF-α, and M2 macrophages, by its specific CD163 antibody. The CD68 + / CD163 + ratio was adopted to distinguish between the two macrophage subpopulations. Clinical, radiographic, symptomatology, treatment, and morphological parameters of lesions were collected and a significance level of p = 0.05 was adopted for statistical analysis. The results showed that the CD68 + /CD163 + ratio was higher in the RCs (median = 1.22, p = 0.002), and the highest TNF-α immunostaining scores were found in RCs (p = 0.018); in PGs, the CD68 + /CD163 + ratio was lower and associated with a greater CD163 + immunostaining (median = 1.02, p <0.001). The TNF-α in cyst epithelium had a score of 3 in 10 cases and predominance of M1 macrophages by CD68 + /CD163 + (median = 2.23). In addition, CD68 + cells had higher percentage of immunostaining in smaller RCs (p = 0.034). Our findings suggest that increased CD68 immunostaining associated with TNF-α cytokine in RCs results in a greater differentiation of the M1 phenotype. The higher CD163 immunostaining in PGs results in greater differentiation of the M2 phenotype. Therefore, the inflammatory state promoted by M1 macrophages is related to growth and progression of RCs; on the other hand, the immunomodulatory state of M2 macrophages is related to maintenance of PGs.

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Section: Declaration Of Interestsmentioning

confidence: 98%

Macrophages subpopulations in chronic periapical lesions according to clinical and morphological aspects

et al. 2019

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“…Diffuse distribution of CD68+ cells was observed in the connective tissue of PGs and RCs, corroborating the findings of Suzuki et al (2001). Bracks et al (2014 and Cassanta et al (2017) detected a larger number of CD68+ cells in areas of active inflammation, especially in central areas of PGs and in the subepithelial region of RCs.…”

Section: Discussionmentioning

confidence: 96%

“…These cells represent the first line of local defense, being not only involved in phagocytosis but also in the production of inflammatory mediators in response to bacterial proliferation in the root canals (Lin et al 2000;Azeredo et al 2017;Cassanta et al 2017). This analysis suggests that macrophages are responsible for the development, maintenance and/or severity of the inflammatory process in these lesions.…”

Section: Discussionmentioning

confidence: 96%

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Immunohistochemical expression of macrophages in chronic periapical lesions

Farias

Cavalcante

Lima

et al. 2021

RSD

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Objective: To analyze the expression of macrophages in periapical granulomas (PGs) and radicular cysts (RCs). Methodology: We selected 264 cases of chronic periapical lesions stored at the Laboratory of Pathology, Dental School of Pernambuco (FOP)/UPE, including 89 PGs and 175 RCs. Seventy-nine cases, 23 PGs and 56 RCs, were submitted to immunohistochemical analysis by the streptavidin-biotin method using anti-CD68 antibody. The chi-square and Fisher’s exact tests were used to determine the existence of associations with categorical and clinical variables, adopting a 95% confidence level (p≤0.05). Results: We observed immunoexpression of CD68 in 83% of cases. The number of CD68+ cells (score 3 or 4) was higher in PGs, with predominantly intense staining. Significant differences in the number of CD68+ cells and staining intensity were observed between the chronic periapical lesions analyzed. Conclusion: The presence of CD68+ cells in periapical tissues may indicate the development, maintenance and/or severity of the inflammation-mediated immune response, which is more intense in PG.

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“…Accelerated inflammation by activated macrophages results due to generation of nitric oxide by (NOS). [ 12 13 14 ] Metformin pharmacologically modulates the iNOS/NO pathway[ 15 ] thereby attenuating the progression of apical periodontitis. [ 13 ] Metformin additionally suppresses iNOS expression induced by Lipopolysaccharide (LPS).…”

Section: Etforminmentioning

confidence: 99%

Drug Repurposing for Tooth Regeneration

Divya

Muddappa

Singh

et al. 2021

Journal of Pharmacy and Bioallied Sciences

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Drug repurposing which identifies new therapeutic use(s) for drugs currently in use is a brand-new avenue of research interest worldwide. It circumvents the high-end monetary and time investment usually associated with contemporary drug discoveries. In the field of dentistry, recent studies in drug repurposing focuses in attaining dentin repair or reduction of bone resorption associated with apical periodontitis. Metformin, an anti-diabetic drug has shown pro-osteogenic properties. Aspirin a known anti-inflammatory agent with anticoagulant action is found to modulate the differentiation of dental pulp cells. The significant role of glycogen synthase kinase-3 inhibitors in activating the Wnt/-beta cat signaling pathway of mesenchymal pulp stem cells may pave the way to the pharmacological treatment of dental caries in near future. It is to be noted here that further preclinical and clinical studies are warranted for the regular therapeutic use of these potential drugs in clinical dentistry.

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Modulation of Matrix Metalloproteinase 14, Tissue Inhibitor of Metalloproteinase 3, Tissue Inhibitor of Metalloproteinase 4, and Inducible Nitric Oxide Synthase in the Development of Periapical Lesions

Cited by 13 publications

References 31 publications

Macrophages subpopulations in chronic periapical lesions according to clinical and morphological aspects

Macrophages subpopulations in chronic periapical lesions according to clinical and morphological aspects

Immunohistochemical expression of macrophages in chronic periapical lesions

Drug Repurposing for Tooth Regeneration

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