PMID- 37993094
OWN - NLM
STAT- MEDLINE
DCOM- 20240216
LR  - 20240216
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 336
DP  - 2024 Jan 1
TI  - TET1-mediated epigenetic regulation of tumor necrosis factor-alpha in trigeminal 
      ganglia contributes to chronic temporomandibular joint pain.
PG  - 122283
LID - S0024-3205(23)00918-9 [pii]
LID - 10.1016/j.lfs.2023.122283 [doi]
AB  - Chronic temporomandibular joint (TMJ) pain profoundly affects patients' quality 
      of life. Trigeminal tumor necrosis factor-alpha (TNFalpha) plays a pivotal role in 
      mediating TMJ pain in mice, yet the underlying epigenetic mechanisms remain 
      enigmatic. To unravel these epigenetic intricacies, we employed a multifaceted 
      approach. Hydroxymethylated DNA immunoprecipitation (hMeDIP) and chromatin 
      immunoprecipitation (ChIP) followed by qPCR were employed to investigate the 
      demethylation of TNFalpha gene (Tnfa) and its regulation by ten-eleven translocation 
      methylcytosine dioxygenase 1 (TET1) in a chronic TMJ pain mouse model. The global 
      levels of 5-hydroxymethylcytosine (5hmc) and percentage of 5hmc at the Tnfa 
      promoter region were measured in the trigeminal ganglia (TG) and spinal 
      trigeminal nucleus caudalis (Sp5C) following complete Freund's adjuvant (CFA) or 
      saline treatment. TET1 knockdown and pain behavioral testing were conducted to 
      ascertain the role of TET1-mediated epigenetic regulation of TNFalpha in the 
      pathogenesis of chronic TMJ pain. Our finding revealed an increase in 5hmc at the 
      Tnfa promoter region in both TG and Sp5C of CFA-treated mice. TET1 was 
      upregulated in the mouse TG, and the ChIP result showed TET1 direct binding to 
      the Tnfa promoter, with higher efficiency in the CFA-treated group. 
      Immunofluorescence revealed the predominant expression of TET1 in trigeminal 
      neurons. TET1 knockdown in the TG significantly reversed CFA-induced TNFalpha 
      upregulation and alleviated chronic TMJ pain. In conclusion, our study implicates 
      TET1 as a vital epigenetic regulator contributing to chronic inflammatory TMJ 
      pain via trigeminal TNFalpha signaling. Targeting TET1 holds promise for epigenetic 
      interventions in TMJ pain management.
CI  - Copyright (c) 2023. Published by Elsevier Inc.
FAU - Wang, Zhitao
AU  - Wang Z
AD  - Department of Anesthesiology and Perioperative Medicine, The Second Affiliated 
      Hospital of Zhengzhou University, Zhengzhou, Henan, China.
FAU - Ma, Heng
AU  - Ma H
AD  - Department of Anesthesiology and Perioperative Medicine, The Second Affiliated 
      Hospital of Zhengzhou University, Zhengzhou, Henan, China.
FAU - Nasir, Abdul
AU  - Nasir A
AD  - Department of Anesthesiology and Perioperative Medicine, The Second Affiliated 
      Hospital of Zhengzhou University, Zhengzhou, Henan, China; Medical Research 
      Center, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 
      China.
FAU - Liu, Sufang
AU  - Liu S
AD  - Department of Biomedical Sciences, Texas A&M University College of Dentistry, 
      Dallas, TX, USA.
FAU - Li, Zhisong
AU  - Li Z
AD  - Department of Anesthesiology and Perioperative Medicine, The Second Affiliated 
      Hospital of Zhengzhou University, Zhengzhou, Henan, China.
FAU - Tao, Feng
AU  - Tao F
AD  - Department of Biomedical Sciences, Texas A&M University College of Dentistry, 
      Dallas, TX, USA. Electronic address: ftao81@tamu.edu.
FAU - Bai, Qian
AU  - Bai Q
AD  - Department of Anesthesiology and Perioperative Medicine, The Second Affiliated 
      Hospital of Zhengzhou University, Zhengzhou, Henan, China; Medical Research 
      Center, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 
      China. Electronic address: baiqian@zzu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20231120
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (TET1 protein, mouse)
RN  - 0 (DNA-Binding Proteins)
RN  - 9007-81-2 (Freund's Adjuvant)
SB  - IM
MH  - *Tumor Necrosis Factor-alpha/genetics/metabolism
MH  - Epigenesis, Genetic/genetics
MH  - *DNA-Binding Proteins/metabolism
MH  - *Trigeminal Ganglion/physiopathology
MH  - *Arthralgia/chemically induced/physiopathology
MH  - *Temporomandibular Joint/physiopathology
MH  - Male
MH  - Animals
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Freund's Adjuvant/pharmacology
MH  - Up-Regulation/drug effects
MH  - Neurons/metabolism
MH  - Gene Knockdown Techniques
MH  - Promoter Regions, Genetic
MH  - Protein Binding/drug effects
OTO - NOTNLM
OT  - Spinal trigeminal nucleus caudalis
OT  - Temporomandibular joint pain
OT  - Ten-eleven translocation methylcytosine dioxygenase
OT  - Trigeminal ganglia
OT  - Tumor necrosis factor-alpha
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/11/23 00:42
MHDA- 2023/12/25 06:42
CRDT- 2023/11/22 19:33
PHST- 2023/10/03 00:00 [received]
PHST- 2023/11/15 00:00 [revised]
PHST- 2023/11/19 00:00 [accepted]
PHST- 2023/12/25 06:42 [medline]
PHST- 2023/11/23 00:42 [pubmed]
PHST- 2023/11/22 19:33 [entrez]
AID - S0024-3205(23)00918-9 [pii]
AID - 10.1016/j.lfs.2023.122283 [doi]
PST - ppublish
SO  - Life Sci. 2024 Jan 1;336:122283. doi: 10.1016/j.lfs.2023.122283. Epub 2023 Nov 
      20.