PMID- 23368949
OWN - NLM
STAT- MEDLINE
DCOM- 20140829
LR  - 20211021
IS  - 1943-3670 (Electronic)
IS  - 0022-3492 (Print)
IS  - 0022-3492 (Linking)
VI  - 84
IP  - 11
DP  - 2013 Nov
TI  - Epigenetic regulation of TNFA expression in periodontal disease.
PG  - 1606-16
LID - 10.1902/jop.2013.120294 [doi]
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the molecular 
      pathogenesis of periodontal disease. However, the epigenetic regulation 
      attributable to microbial and inflammatory signals at the biofilm-gingival 
      interface are poorly understood. In this study, the DNA methylation alteration 
      within the TNFA promoter in human gingival biopsies from different stages of 
      periodontal disease is investigated and the regulatory mechanism of TNFA 
      transcription by DNA methylation is explored. METHODS: Gingival biopsies were 
      obtained from 17 patients with chronic periodontitis (CP) and 18 periodontally 
      healthy individuals. Another 11 individuals participated in an experimentally 
      induced gingivitis study, and gingival biopsies were collected at the baseline, 
      induction, and resolution phase. To confirm that TNFA promoter methylation 
      modulated TNFA transcription, THP.1 cells were treated with a DNA 
      methyltransferase inhibitor, 5-Aza-2-deoxycytidine (5-Aza-2dC), and an RAW294.7 
      cell line transfected with a TNFA promoter-specific luciferase reporter system 
      with or without methylation was used. RESULTS: In gingival biopsies from 
      individuals with severe CP, two individual cytosine-guanine dinucleotides (CpG 
      sites) within the TNFA promoter (at -163 and -161 bp) displayed increased 
      methylation in CP samples compared to those with gingival health (16.1% +/- 5.1% 
      versus 11.0% +/- 4.6%, P = 0.02 and 19.8% +/- 4.1% versus 15.4% +/- 3.6%, P = 0.04, 
      respectively). The methylation level at -163 bp was inversely associated with the 
      transcription level of TNFA (P = 0.018). However, no significant difference in 
      the TNFA promoter methylation pattern was observed in samples biopsied during the 
      induction or resolution phase of experimentally induced gingivitis, which 
      represented a reversible periodontal lesion. THP.1 cells treated with 5-Aza-2dC 
      demonstrated a time-dependent increase in TNFA messenger level. It was also found 
      that the luciferase activity decreased 2.6-fold in a construct containing an in 
      vitro methylated TNFA promoter when compared to the unmethylated insert (P = 
      0.03). CONCLUSION: Although the biopsy samples represented a mixed cell 
      population, the change in promoter methylation status in chronic periodontal 
      disease suggested that DNA methylation may be an important regulatory mechanism 
      in controlling TNFA transcriptional expression in periodontal disease.
FAU - Zhang, Shaoping
AU  - Zhang S
AD  - Center for Oral and Systemic Diseases, School of Dentistry, University of North 
      Carolina at Chapel Hill, Chapel Hill, NC.
FAU - Barros, Silvana P
AU  - Barros SP
FAU - Moretti, Antonio J
AU  - Moretti AJ
FAU - Yu, Ning
AU  - Yu N
FAU - Zhou, Jing
AU  - Zhou J
FAU - Preisser, John S
AU  - Preisser JS
FAU - Niculescu, Mihai D
AU  - Niculescu MD
FAU - Offenbacher, Steven
AU  - Offenbacher S
LA  - eng
GR  - R90 DE022527/DE/NIDCR NIH HHS/United States
GR  - RR00046/RR/NCRR NIH HHS/United States
GR  - UL1 TR001111/TR/NCATS NIH HHS/United States
GR  - M01 RR000046/RR/NCRR NIH HHS/United States
GR  - UL1RR025747/RR/NCRR NIH HHS/United States
GR  - UL1 RR025747/RR/NCRR NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130131
PL  - United States
TA  - J Periodontol
JT  - Journal of periodontology
JID - 8000345
RN  - 0 (Luminescent Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 776B62CQ27 (Decitabine)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.1.1.- (DNA Modification Methylases)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Adult
MH  - Azacitidine/analogs & derivatives/pharmacology
MH  - Biopsy
MH  - Campylobacter rectus/immunology
MH  - Cell Culture Techniques
MH  - Cell Line
MH  - Chronic Periodontitis/*genetics/immunology/pathology
MH  - CpG Islands/genetics
MH  - Cross-Sectional Studies
MH  - DNA Methylation/genetics
MH  - DNA Modification Methylases/antagonists & inhibitors
MH  - Decitabine
MH  - Epigenesis, Genetic/*genetics
MH  - Female
MH  - Gene Expression Regulation/genetics
MH  - Gingivitis/genetics/immunology/pathology
MH  - Humans
MH  - Luciferases
MH  - Luminescent Agents
MH  - Male
MH  - Middle Aged
MH  - Monocytes/drug effects/immunology/microbiology
MH  - Osteoclasts/cytology
MH  - Promoter Regions, Genetic/genetics
MH  - RNA, Messenger/genetics
MH  - Transcription, Genetic/genetics
MH  - Transfection/methods
MH  - Tumor Necrosis Factor-alpha/*genetics
MH  - Young Adult
PMC - PMC3986590
MID - NIHMS452354
EDAT- 2013/02/02 06:00
MHDA- 2014/08/30 06:00
PMCR- 2014/04/15
CRDT- 2013/02/02 06:00
PHST- 2013/02/02 06:00 [entrez]
PHST- 2013/02/02 06:00 [pubmed]
PHST- 2014/08/30 06:00 [medline]
PHST- 2014/04/15 00:00 [pmc-release]
AID - 10.1902/jop.2013.120294 [doi]
PST - ppublish
SO  - J Periodontol. 2013 Nov;84(11):1606-16. doi: 10.1902/jop.2013.120294. Epub 2013 
      Jan 31.