Immune response mediated by Th1 / IL-17 / caspase-9 promotes evolution of periodontal disease

Sommer, MA; Dalia, Rodrigo Augusto; Nogueira, Andressa Vilas Boas; Cirelli, Joni Augusto; Vinolo, Marco Aurélio Ramirez; Fachi, José Luís; Oliveira, Camila Andréa de; Andrade, Thiago Antônio Moretti de; Mendonça, Fernanda Aparecida Sampaio; Santamaria, Milton; Felonato, Maíra

doi:10.1016/j.archoralbio.2018.09.009

Cited by 27 publications

(23 citation statements)

References 35 publications

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“…The development of periodontitis is tied to the accumulation of inflammatory mediators including TNF-α and INF-γ, and an increased inflammatory response develops with the destruction of periodontium tissue. 49 In our study, the inflammatory factors TNF-α and INF-γ were used to mimic an inflammatory condition. We found that the CB1 expression level in PDLSCs was decreased after stimulation with either of these inflammatory factors.…”

Section: Discussionmentioning

confidence: 99%

CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment

et al. 2019

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Objectives Periodontitis is an inflammatory immune disease that causes periodontal tissue loss. Inflammatory immunity and bone metabolism are closely related to periodontitis. The cannabinoid receptor I (CB1) is an important constituent of the endocannabinoid system and participates in bone metabolism and inflammation tissue healing. It is unclear whether CB1 affects the mesenchymal stem cell (MSC) function involved in periodontal tissue regeneration. In this study, we revealed the role and mechanism of CB1 in the osteo/dentinogenic differentiation of periodontal ligament stem cells (PDLSCs) in an inflammatory environment. Materials and methods Alkaline phosphatase (ALP) activity, Alizarin Red staining, quantitative calcium analysis and osteo/dentinogenic markers were used to assess osteo/dentinogenic differentiation. Real‐time RT‐PCR and Western blotting were employed to detect gene expression. Results CB1 overexpression or CB1 agonist (10 µM R‐1 Meth) promoted the osteo/dentinogenic differentiation of PDLSCs. Deletion of CB1 or the application of CB1 antagonist (10 µM AM251) repressed the osteo/dentinogenic differentiation of PDLSCs. The activation of CB1 enhanced the TNF‐α‐ and INF‐γ‐impaired osteo/dentinogenic differentiation potential in PDLSCs. Moreover, CB1 activated p38 MAPK and JNK signalling and repressed PPAR‐γ and Erk1/2 signalling. Inhibition of JNK signalling could block CB1‐activated JNK and p38 MAPK signalling, while CB1 could activate p38 MAPK and JNK signalling, which was inhibited by TNF‐α and INF‐γ stimulation. Conclusions CB1 was able to enhance the osteo/dentinogenic differentiation ability of PDLSCs via p38 MAPK and JNK signalling in an inflammatory environment, which might be a potential target for periodontitis treatment.

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Section: Discussionmentioning

confidence: 99%

CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment

et al. 2019

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“…Indeed, mice strains selected for maximal inflammatory response, characterized by high levels of multiple proinflammatory cytokines, present an accelerated lesion progression rate (Trombone et al 2010). The prototypic Th1 cytokine interferon-γ (IFN-γ) inhibits osteoclastogenesis in vitro; however, its prominent proinflammatory effect in vivo seems to overcome the inhibitory effect, leading to increased bone resorption (Garlet et al 2008; Sommer et al 2019). Indeed, IFN-γ contributes to lesion progression via induction of chemokine expression and the consequent chemoattraction of RANKL-producing cells and osteoclast precursors to the lesion environment (Garlet et al 2008; Sommer et al 2019).…”

Section: Host Response Determinants Of Lesion Progression and Stabilitymentioning

confidence: 99%

“…The prototypic Th1 cytokine interferon-γ (IFN-γ) inhibits osteoclastogenesis in vitro; however, its prominent proinflammatory effect in vivo seems to overcome the inhibitory effect, leading to increased bone resorption (Garlet et al 2008; Sommer et al 2019). Indeed, IFN-γ contributes to lesion progression via induction of chemokine expression and the consequent chemoattraction of RANKL-producing cells and osteoclast precursors to the lesion environment (Garlet et al 2008; Sommer et al 2019). In addition, Th17 and B cells are described as osteoclastogenic subsets implicated in inflammatory osteolytic conditions via RANKL upregulation and boost of neutrophils and/or macrophages activity (Dutzan, Gamonal, et al 2009; Abe et al 2015; Sommer et al 2019).…”

Section: Host Response Determinants Of Lesion Progression and Stabilitymentioning

confidence: 99%

Determinants of Periodontal/Periapical Lesion Stability and Progression

et al. 2020

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Periodontal and periapical lesions are infectious inflammatory osteolitytic conditions in which a complex inflammatory immune response mediates bone destruction. However, the uncertainty of a lesion’s progressive or stable phenotype complicates understanding of the cellular and molecular mechanisms triggering lesion activity. Evidence from clinical and preclinical studies of both periodontal and periapical lesions points to a high receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) ratio as the primary determinant of osteolytic activity, while a low RANKL/OPG ratio is often observed in inactive lesions. Proinflammatory cytokines directly modulate RANKL/OPG expression and consequently drive lesion progression, along with pro-osteoclastogenic support provided by Th1, Th17, and B cells. Conversely, the cooperative action between Th2 and Tregs subsets creates an anti-inflammatory and proreparative milieu associated with lesion stability. Interestingly, the trigger for lesion status switch from active to inactive can originate from an unanticipated RANKL immunoregulatory feedback, involving the induction of Tregs and a host response outcome with immunological tolerance features. In this context, dendritic cells (DCs) appear as potential determinants of host response switch, since RANKL imprint a tolerogenic phenotype in DCs, described to be involved in both Tregs and immunological tolerance generation. The tolerance state systemically and locally suppresses the development of exacerbated and pathogenic responses and contributes to lesions stability. However, immunological tolerance break by comorbidities or dysbiosis could explain lesions relapse toward activity. Therefore, this article will provide a critical review of the current knowledge concerning periodontal and periapical lesions activity and the underlying molecular mechanisms associated with the host response. Further studies are required to unravel the role of immunological responsiveness or tolerance in the determination of lesion status, as well as the potential cooperative and/or inhibitory interplay among effector cells and their impact on RANKL/OPG balance and lesion outcome.

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“…It was demonstrated that high inflammatory responses are associated to increased CASP9 activity and this process may be involved in the progression of inflammatory conditions, such as periodontitis and acute liver disease [84,85]. Furthermore, variants of CASP9 have been associated with cancer [86].…”

Section: Intrinsic Pathwaymentioning

confidence: 99%

A Cell’s Fate: An Overview of the Molecular Biology and Genetics of Apoptosis

Cavalcante

Schaan

Cabral

et al. 2019

IJMS

124

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Apoptosis is one of the main types of regulated cell death, a complex process that can be triggered by external or internal stimuli, which activate the extrinsic or the intrinsic pathway, respectively. Among various factors involved in apoptosis, several genes and their interactive networks are crucial regulators of the outcomes of each apoptotic phase. Furthermore, mitochondria are key players in determining the way by which cells will react to internal stress stimuli, thus being the main contributor of the intrinsic pathway, in addition to providing energy for the whole process. Other factors that have been reported as important players of this intricate molecular network are miRNAs, which regulate the genes involved in the apoptotic process. Imbalance in any of these mechanisms can lead to the development of several illnesses, hence, an overall understanding of these processes is essential for the comprehension of such situations. Although apoptosis has been widely studied, the current literature lacks an updated and more general overview on this subject. Therefore, here, we review and discuss the mechanisms of apoptosis, highlighting the roles of genes, miRNAs, and mitochondria involved in this type of cell death.

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Immune response mediated by Th1 / IL-17 / caspase-9 promotes evolution of periodontal disease

Cited by 27 publications

References 35 publications

CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment

CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment

Determinants of Periodontal/Periapical Lesion Stability and Progression

A Cell’s Fate: An Overview of the Molecular Biology and Genetics of Apoptosis

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