Differential expression of inflammasome regulatory transcripts in periodontal disease

Aral, Kübra; Berdeli, Eynar; Cooper, Paul R.; Milward, Michael; Kapila, Yvonne L.; Ünal, Beyza Karadede; Aral, Cüneyt Asım; Berdelı, Afig

doi:10.1002/jper.19-0222

Cited by 49 publications

(47 citation statements)

References 36 publications

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“…There is evidence that COPs and POPs are lacking in inflammatory diseases. For instance, CAPS and sepsis patients have significantly less POP1 expression in whole blood than healthy controls [149], POP1, POP2, and CARD18 are downregulated in periodontal disease [165] and CARD18 is highly expressed in the epidermis, but expression is lost in lichen planus [166]. Hence, we expect that there is a unique expression pattern of POPs and COPs in different tissues and cell types, either during homeostasis or during inflammatory immune responses.…”

Section: Discussionmentioning

confidence: 99%

An Update on CARD Only Proteins (COPs) and PYD Only Proteins (POPs) as Inflammasome Regulators

Devi

Stehlik

Dorfleutner

2020

IJMS

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Inflammasomes are protein scaffolds required for the activation of caspase-1 and the subsequent release of interleukin (IL)-1β, IL-18, and danger signals, as well as the induction of pyroptotic cell death to restore homeostasis following infection and sterile tissue damage. However, excessive inflammasome activation also causes detrimental inflammatory disease. Therefore, extensive control mechanisms are necessary to prevent improper inflammasome responses and inflammatory disease. Inflammasomes are assembled by sequential nucleated polymerization of Pyrin domain (PYD) and caspase recruitment domain (CARD)-containing inflammasome components. Once polymerization is nucleated, this process proceeds in a self-perpetuating manner and represents a point of no return. Therefore, regulation of this key step is crucial for a controlled inflammasome response. Here, we provide an update on two single domain protein families containing either a PYD or a CARD, the PYD-only proteins (POPs) and CARD-only proteins (COPs), respectively. Their structure allows them to occupy and block access to key protein–protein interaction domains necessary for inflammasome assembly, thereby regulating the threshold of these nucleated polymerization events, and consequently, the inflammatory host response.

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Section: Discussionmentioning

confidence: 99%

An Update on CARD Only Proteins (COPs) and PYD Only Proteins (POPs) as Inflammasome Regulators

Devi

Stehlik

Dorfleutner

2020

IJMS

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“…The NLRP3 mutated allele (C) is a variant in the intron 7 of chromosome 1q44 and was previously correlated to the higher transcriptional activity of the gene when compared to the wild T allele [61]. An over expression of the NLRP3 inflammasome and a downregulation of NLRP3 inhibitors were observed in the gingival tissue of patients with PD [28,31,39]. The NLRP3 activation depends on signals provided by recognition of PAMPs, such as microbial lipopolysaccharides (LPS), and DAMPs (ie.…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of NLRP3 in the gingival tissue and increased salivary levels of NLRP3 were observed in PD patients [30]. Upregulation of the inflammasome may lead to an increase in IL-1β production [31,32]. Some therapeutic pathways, based on inhibition of the NLRP3 inflammasome, have been effective in the treatment of experimental diabetic periodontitis, inflammatory diseases and osteoarthritis [33][34][35].…”

Section: Introductionmentioning

confidence: 99%

“…Some therapeutic pathways, based on inhibition of the NLRP3 inflammasome, have been effective in the treatment of experimental diabetic periodontitis, inflammatory diseases and osteoarthritis [33][34][35]. NLRP1, NLRP2, NLRC4 and AIM2 were also evaluated in PD, however the results about their expression in periodontal tissue were controversial [31,32,[36][37][38][39][40].…”

Section: Introductionmentioning

confidence: 99%

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Influence of inflammasome NLRP3, and IL1B and IL2 gene polymorphisms in periodontitis susceptibility

et al. 2020

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The pathogenesis of periodontitis (PD) involves several molecules of the immune system that interact in a network to eliminate the periodontopathogens, yet, they contribute to periodontal tissue destruction. The different mechanisms that lead to periodontal tissue damage are not clear. Despite this, immune response genes have been related to the development of PD previously, such as those involved in inflammasomes which are multiprotein complexes and cytokines including Interleukin-1. The aim of the study was to evaluate the polymorphisms in NLRP3 inflammasome, cytokine and receptor of cytokines genes in the development of periodontitis. This case-control study was conducted in 186 patients with PD (stage II and III and grade B) and 208 controls (localized gingivitis and periodontally healthy individuals). Genotyping was performed using PCR-RFLP for the SNP rs4612666 in NLRP3 and using PCR-SSP for IL1A,

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“…Previous studies have de ned the functions of TRIM16 in several biological processes; Recently, signi cant downregulation of TRIM16 was observed in periodontal tissue of patients with periodontitis compared with tissues in healthy individuals [26]. We speculated the impaired osteogenic capacity of hPDLSCsin in ammatory microenvironment might be associated with lower expression of TRIM16.…”

Section: Introductionmentioning

confidence: 91%

TRIM16 Positively Regulates Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating the Ubiquitination and Degradation of RUNX2

Zhao

Zhai

Liu

et al. 2020

Preprint

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Abstract BackgroundPeriodontal disease is a common disease that compromises the integrity of tooth-supporting tissues. Bone regeneration is the ultimate goal of periodontal therapies, in which osteogenic differentiation of human periodontal ligament stem cells plays a critical role. The tripartite motif (TRIM)16 is downregulated in periodontal tissues of patients with periodontitis and involved in osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs).However, the role of TRIM16 in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is largely unknown.MethodshPDLSCs were isolated and identified by immunophenotype assays using flow cytometry. Overexpression plasmids and specific short-hairpin RNAs (shRNAs) were constructed to manipulate the expression of target molecules. Alkaline phosphatase (ALP) staining, alizarin red staining (ARS) and enzyme‐linked immunosorbent assays (ELISA) were used to evaluate osteogenic potential capacity. Reverse transcription quantitative PCR (RT-qPCR) and Western blot analysis were performed to determine the expression of osteogenic-related markers and activation of relevant signaling pathways. Co-immunoprecipitation assays were performed to confirm the interactions between proteins and the ubiquitination of RUNX2. A LC-MS/MS analysis was performed to explore the different expression proteins in present of TRIM16.ResultsTRIM16 significantly promoted alkaline phosphatase activity and mineralized nodule formation, and positively regulated the osteogenic differentiation of hPDLSCs by enhancing protein expression of RUNX2, COL1A1 and OCN. Mechanistically, TRIM16 serves as a pivotal factor that stabilizes RUNX2 protein levels by decreasing CHIP-mediated K48-linked ubiquitination degradation of the RUNX2 protein. Besides, TRIM16 significantly increased expression of COL1A1 via activation of p38MAPK/RUNX2.ConclusionThis study identified a novel mechanism of TRIM16 in regulating stability of the RUNX2 protein, which may promote the osteogenic differentiation of hPDLSCs. TRIM16 may be a potential target of stem cell based-bone regeneration for periodontal therapies.

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Differential expression of inflammasome regulatory transcripts in periodontal disease

Cited by 49 publications

References 36 publications

An Update on CARD Only Proteins (COPs) and PYD Only Proteins (POPs) as Inflammasome Regulators

An Update on CARD Only Proteins (COPs) and PYD Only Proteins (POPs) as Inflammasome Regulators

Influence of inflammasome NLRP3, and IL1B and IL2 gene polymorphisms in periodontitis susceptibility

TRIM16 Positively Regulates Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating the Ubiquitination and Degradation of RUNX2

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