Krüppel-like factor 5 -mediated Sirtuin6 promotes osteogenic differentiation and inhibits inflammatory injury of lipopolysaccharide-induced periodontal membrane stem cells by inhibiting nuclear factor kappa-B pathway

Li, Chanxiu; Xiao, Feng; Wen, Yunsheng; Wu, Jian; Huang, Nannan

doi:10.1080/21655979.2022.2036915

Cited by 11 publications

(5 citation statements)

References 41 publications

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“…Studies have shown that Pg‐LPS‐induced inflammation can inhibit osteogenic differentiation of periodontal ligament stem cells, and our results further confirm this conclusion 36,37 . hPDLSCs were isolated according to previous studies and passaged after the cells had crawled out and reached 90% confluence.…”

Section: Resultssupporting

confidence: 86%

“…Studies have shown that Pg-LPS-induced inflammation can inhibit osteogenic differentiation of periodontal ligament stem cells, and our results further confirm this conclusion. 36,37 hPDLSCs were isolated according to previous studies and passaged after the cells had crawled out and reached 90% confluence. When hPDLSCs were stimulated with 10 μg/mL Pg-LPS for 7 days, qRT-PCR demonstrated that Pg-LPS stimulation increased the mRNA expression of IL-6 and IL-8, which are inflammatory markers (Figure 4A).…”

Section: Pg-lps-induced Inflammation Can Inhibit Osteogenic Different...mentioning

confidence: 99%

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Identifying genes for regulating osteogenic differentiation of human periodontal ligament stem cells in inflammatory environments by bioinformatics analysis

Wang,

Yang,

Wang

et al. 2023

J of Periodontal Research

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Background and ObjectivesPeriodontitis is an immuno‐inflammatory disease caused by dental plaque biofilms and inflammations. The regeneration of bone tissue in inflammatory environment is of great significance for the treatment of periodontal disease, but the specific molecular mechanism of bone formation in periodontitis still needs further exploration. The objective of this study was to identify key osteogenesis‐related genes (ORGs) in periodontitis.MethodsWe used two datasets from the Gene Expression Omnibus (GEO) database to find differentially expressed mRNAs and miRNAs, further performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then we predicted the downstream genes of the differentially expressed miRNAs (DEMs) by the TargetScan database and established a miRNA‐mRNA regulatory network. Finally, the osteogenic mechanism of periodontitis was explored through quantitative real‐time PCR (qRT‐PCR) by inducing inflammatory environment and osteogenic differentiation of hPDLSCs.ResultsThrough differential expression analysis and prediction of downstream target genes of DEMs, we created a miRNA‐mRNA regulatory network consisting of 29 DEMs and 11 differentially expressed osteogenesis‐related genes (DEORGs). In addition, the qRT‐PCR results demonstrated that BTBD3, PLAT, AKAP12, SGK1, and GLCE expression levels were significantly upregulated, while those of TIMP3, ZCCHC14, LIN7A, DNAH6, NNT, and ITGA6 were downregulated under the dual effects of inflammatory stimulation and osteogenic induction.ConclusionDEORGs might be important factors in the osteogenic phase of periodontitis, and the miRNA‐mRNA network may shed light on the clarification of the role and mechanism of osteogenesis in periodontitis and contribute to the development of novel therapeutic strategies.

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Section: Resultssupporting

confidence: 86%

Section: Pg-lps-induced Inflammation Can Inhibit Osteogenic Different...mentioning

confidence: 99%

Identifying genes for regulating osteogenic differentiation of human periodontal ligament stem cells in inflammatory environments by bioinformatics analysis

Wang,

Yang,

Wang

et al. 2023

J of Periodontal Research

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“…Huang et al showed that increased SIRT6 suppresses cementoblast differentiation and mineralization through the inhibition of glucose transporter 1 (GLUT1), a glucose transporter necessary in cementogenesis, as well as activation of AMPK pathway (Huang et al, 2019). Interestingly, SIRT6 overexpression also promotes osteogenic differentiation and inhibits LPS-induced inflammatory response via suppressing NF-κB pathway in a periodontitis mode constructed by PDLSCs, which could be transcriptionally activated by Krüppel-like factor 5 (KLF5) (Li et al, 2022).…”

Section: Sirtuins In Oral Infectious and Inflammatory Diseases Period...mentioning

confidence: 99%

Oxidative stress and inflammation regulation of sirtuins: New insights into common oral diseases

et al. 2022

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Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylases, comprising seven members SIRT1-SIRT7. Sirtuins have been extensively studied in regulating ageing and age-related diseases. Sirtuins are also pivotal modulators in oxidative stress and inflammation, as they can regulate the expression and activation of downstream transcriptional factors (such as Forkhead box protein O3 (FOXO3a), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB)) as well as antioxidant enzymes, through epigenetic modification and post-translational modification. Most importantly, studies have shown that aberrant sirtuins are involved in the pathogenesis of infectious and inflammatory oral diseases, and oral cancer. In this review, we provide a comprehensive overview of the regulatory patterns of sirtuins at multiple levels, and the essential roles of sirtuins in regulating inflammation, oxidative stress, and bone metabolism. We summarize the involvement of sirtuins in several oral diseases such as periodontitis, apical periodontitis, pulpitis, oral candidiasis, oral herpesvirus infections, dental fluorosis, and oral cancer. At last, we discuss the potential utilization of sirtuins as therapeutic targets in oral diseases.

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“…Additionally, SIRT6 de ciency was associated with activation of NF-κB pathway in LPS-induced human dental pulp cell [36]. A recent study by Li et al (2022), demonstrated that SIRT6 supresses the in ammatory response of LPS-induced PDLCs via inhibiting NF-κB pathway and, it promotes osteogenic differentiation and viability [25]. PDLCs represent local immune cells of the periodontal tissues and SIRT6 may have possible role of development periodontitis via NF-κB pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies reported that the development of apical periodontitis is correlated by decreased expression of SIRT6 and that SIRT6 may reduce periapical lesions by inhibiting apoptosis [23,24]. A recent article revealed that SIRT6 inhibits the in ammatory response of LPS-induced periodontal ligament stem cells (PDLSCs) by inhibiting the nuclear factor κB (NF-κB) pathway, while promoting viability and osteogenic differentiation [25]. The apoptosis mechanism is triggered in the hypoxic environment that occurs as a result of the prolongation of the in ammatory response in the periodontal tissues (chronic in ammation).…”

Section: Introductionmentioning

confidence: 99%

Serum and Saliva Sirtuin 6, Lipoxin A4, Caspase8 Levels in Correlation with Periodontal Status in Severe Periodontitis

Çekici

Sahinkaya

Donmez

et al. 2022

Preprint

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Objectives: It has been stated that Sirtuin-6 (SIRT6) play a important role in regulation of inflammation, energy metabolism, homeostasis and apoptosis, and SIRT6 may be assosiciated with many diseases. The aim of this study was to evaluate saliva and serum SIRT6, Lipoxin A4 (LXA4) and Caspase-8 (CASP8) levels in correlation with periodontal clinical status in patients with periodontitis and healthy subjects. Materials and Methods: 20 patients with Stage III Grade B periodontitis (P) and 20 periodontally healthy individuals (control;C) were included in this study. Clinical periodontal parameters were measured. Saliva and serum levels of SIRT6, LXA4 and CASP8 were analyzed by enzyme-linked immunosorbent assay.Results: Serum SIRT6 and saliva LXA4 levels were significantly lower in the periodontitis group than in the control group (respectively; p=0.010, p= p:0.001). There was no statistically significant difference between the periodontitis and control groups for saliva SIRT6, serum LXA4, serum and saliva CASP8 levels (p>0.05). Significant negative correlations were found between all periodontal clinical parameters (PI, BOP, PPD, CAL) and saliva LXA4 level (p<0.05), and between PPD, CAL, and serum SIRT6 level (respectively; r=-0.465 and r=-0.473, p<0.05). Conclusions: This study demonstrated that significantly lower levels of serum SIRT6 and saliva LXA4 in periodontitis patients and their correlation with periodontal status. Detection of SIRT6 and saliva LXA4 might have a potential role for predicting periodontal status in the future with more precise sampling protocols and with better specifity in testing methods. Clinical Relevance: Serum SIRT6 and saliva LXA4 might be promising biomarkers for monitoring the susceptibility to periodontitis and predicting periodontal status.

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Krüppel-like factor 5 -mediated Sirtuin6 promotes osteogenic differentiation and inhibits inflammatory injury of lipopolysaccharide-induced periodontal membrane stem cells by inhibiting nuclear factor kappa-B pathway

Cited by 11 publications

References 41 publications

Identifying genes for regulating osteogenic differentiation of human periodontal ligament stem cells in inflammatory environments by bioinformatics analysis

Identifying genes for regulating osteogenic differentiation of human periodontal ligament stem cells in inflammatory environments by bioinformatics analysis

Oxidative stress and inflammation regulation of sirtuins: New insights into common oral diseases

Serum and Saliva Sirtuin 6, Lipoxin A4, Caspase8 Levels in Correlation with Periodontal Status in Severe Periodontitis

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