High‐glucose concentration aggravates TNF‐alpha‐induced cell viability reduction in human CD146‐positive periodontal ligament cells via TNFR‐1 gene demethylation

Abstract

Periodontitis is a chronic inflammatory disease that results in the destruction of periodontal soft tissue and the resorption of alveolar bone. Evidence indicates that in diabetic patients, hyperglycemia suppresses periodontal ligament stem cell (PDLSC) functions and leads to difficulties in periodontal repair. The present study aimed to explore the mechanisms by which high‐glucose concentrations aggravate cell viability reduction in human CD146‐positive PDLCs (CD146+PDLCs) under tumor necrosis factor‐alpha (TNF‐alpha) induction. CD146+PDLCs were isolated from periodontal ligament tissues and treated in the absence or presence of 10 ng/ml of TNF‐alpha and 30 mM glucose. Cell viability was detected using Cell Counting Kit‐8 assays and Luminescent Cell Viability Assays. Western blotting and real‐time polymerase chain reaction were performed to determine tumor necrosis factor‐alpha receptor‐1 (TNFR‐1) protein and messenger RNA expression. Bisulfite and MassArray methylation analyses were used to analyze the methylation status of the TNFR‐1 gene. Our results indicated that cell viability was reduced after treatment with a combination of both high‐glucose concentration and TNF‐alpha. Treatment with 30 mM glucose suppressed DNA methyltransferase (DNMT) activities and DNMT1 protein expression, and this was accompanied by the upregulation of TNFR‐1. Additionally, we found that the CpG island located within the TNFR‐1 gene was hypomethylated under 30 mM glucose conditions. S‐adenosylmethionine, an established methyl donor, reversed TNFR‐1 upregulation and restored cell viability against high‐glucose concentration and TNF‐alpha. In conclusion, the present findings suggest that high‐glucose‐induced CpG island hypomethylation within the TNFR‐1 gene plays an essential role in TNFR‐1 upregulation, and this further enhances the cell viability reduction of CD146+PDLCs caused by TNF‐alpha.

circSAMD4A participates in the apoptosis and autophagy of dopaminergic neurons via the miR‑29c‑3p‑mediated AMPK/mTOR pathway in Parkinson's disease

“…In the present study, miR-29c-3p was found to be targeted and regulated by circSAMD4A. Although miR-29c-3p has been reported to participate in the pathogenesis of multiple human diseases, such as colorectal cancer, ovarian cancer and AD (48)(49)(50), to the best of our knowledge, its role in PD has not been previously reported. In the current study, miR-29c-3p was identified to abolish the protective effects of circSAMD4A knockdown against MPTP-or MPP + -induced apoptosis and autophagy.…”

Erythropoietin Activates Autophagy to Regulate Apoptosis and Angiogenesis of Periodontal Ligament Stem Cells via the Akt/ERK1/2/BAD Signaling Pathway under Inflammatory Microenvironment

“…Here, we selected TNF-α to mock the microenvironment of periodontitis, and we established a TNF-α concentration gradient to explore biological behaviors of inflammatory PDLSCs. Coherent with existed literatures [41,45,46], TNF-α inhibited cell viability and increased expression of inflammatory genes via the NF-κB signaling pathway. Fang et al [47] and Meng et al [41] mentioned that TNF-α could also induce apoptosis and oxidative stress of PDLSCs, which was analogous to our study.…”

Micro-Osteoperforations Induce TNF-α Expression and Accelerate Orthodontic Tooth Movement via TNF-α-Responsive Stromal Cells

“…Several studies showed that PDL cells expressed TNFRs [ 38 , 39 , 40 , 41 ]. Furthermore, it has been reported that the expression levels of TNFRs in CD146 positive PDL cells were higher than those in CD146 negative PDL cells, and TNF-α was found to have higher level of biological effect in CD146 positive PDL cells than in CD146 negative PDL cells [ 38 ].…”