PMID- 33641180
OWN - NLM
STAT- MEDLINE
DCOM- 20210518
LR  - 20220531
IS  - 1600-0765 (Electronic)
IS  - 0022-3484 (Linking)
VI  - 56
IP  - 3
DP  - 2021 Jun
TI  - A deficiency of Dec2 triggers periodontal inflammation and pyroptosis.
PG  - 492-500
LID - 10.1111/jre.12849 [doi]
AB  - BACKGROUND AND OBJECTIVES: Periodontal pathogens initiate various diseases and 
      induce inflammatory host responses. The activation of inflammasomes triggers 
      caspase-1 and interleukin (IL)-1beta-mediated pyroptosis via gasdermin D (GSDMD). 
      Differentiated embryo chondrocyte 2 (Dec2) is a transcription repressor that 
      controls the expression of genes involved in innate immune and inflammatory 
      responses. However, the effects of Dec2 on inflammasome-induced pyroptosis in 
      periodontal tissues remain elusive. This study aimed to characterize the 
      activation of Dec2 inflammasomes that contribute to P. gingivalis 
      lipopolysaccharide (LPS)-induced pyroptosis and its functional and regulatory 
      importance in periodontal inflammation. MATERIALS AND METHODS: Human gingival 
      fibroblasts (HGFs) and human periodontal ligament fibroblasts (HPDLFs) were 
      stimulated with P. gingivalis LPS in vitro. An experimental periodontitis mouse 
      model (wild-type (WT) and Dec2KO) was established to profile periodontal 
      pyroptosis. RESULTS: The results demonstrate that P. gingivalis LPS activates 
      caspase-1, caspase-11, and NF-kappaB in HGFs and in HPDLFs. siRNA knockdown of Dec2 
      stimulated the induction and further upregulated LPS-induced pyroptosis in HGFs 
      and HPDLFs, resulting in the release of IL-1beta. Further, a deficiency of Dec2 
      alleviated periodontal pyroptosis via the transcriptional induction of GSDMD. In 
      addition, P. gingivalis-induced IL-1beta expression and Dec2-deficient mice 
      subsequently increased the inflammatory effect of P. gingivalis in HGFs and in 
      HPDLFs, confirming the importance of Dec2 in the activation of inflammasomes and 
      the regulation of pyroptosis. CONCLUSION: Our results demonstrate that Dec2 
      alleviates periodontal pyroptosis by regulating the expression of NF-kappaB, 
      caspase-1 and GSDMD, suggesting that Dec2 is a crucial component of inflammasome 
      activation and subsequent pyroptosis.
CI  - (c) 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Oka, Shunichi
AU  - Oka S
AD  - Department of Anesthesiology, Nihon University School of Dentistry, Tokyo, Japan.
AD  - Division of Immunology and Pathology, Dental Research Center, Nihon University 
      School of Dentistry, Tokyo, Japan.
FAU - Li, Xiaoyan
AU  - Li X
AD  - Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, 
      Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital 
      Medical University School of Stomatology, Beijing, China.
FAU - Sato, Fuyuki
AU  - Sato F
AD  - Pathology Division, Shizuoka Cancer Center, Shizuoka, Japan.
FAU - Zhang, Fengzhu
AU  - Zhang F
AD  - Department of Anesthesiology, Nihon University School of Dentistry at Matsudo, 
      Chiba, Japan.
FAU - Tewari, Nitesh
AU  - Tewari N
AD  - Division of Pedodontics and Preventive Dentistry, Centre for Dental Education and 
      Research, All India Institute of Medical Sciences, New Delhi, India.
FAU - Kim, Il-Shin
AU  - Kim IS
AD  - Department of Dental Hygiene, Honam University, Gwangju, Korea.
FAU - Zhong, Liangjun
AU  - Zhong L
AD  - Department of Stomatology, Hangzhou Normal University, Hangzhou, China.
FAU - Hamada, Nobushiro
AU  - Hamada N
AD  - Division of Microbiology, Department of Oral Science, Graduate School of 
      Dentistry, Kanagawa Dental University, Yokosuka, Japan.
FAU - Makishima, Makoto
AU  - Makishima M
AD  - Division of Biochemistry, Department of Biomedical Sciences, Nihon University 
      School of Medicine, Tokyo, Japan.
FAU - Liu, Yi
AU  - Liu Y
AUID- ORCID: 0000-0002-4998-5547
AD  - Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, 
      Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital 
      Medical University School of Stomatology, Beijing, China.
FAU - Bhawal, Ujjal K
AU  - Bhawal UK
AUID- ORCID: 0000-0002-3746-009X
AD  - Department of Disaster Medicine and Dental Sociology, Kanagawa Dental University, 
      Yokosuka, Japan.
AD  - Department of Biochemistry and Molecular Biology, Nihon University School of 
      Dentistry at Matsudo, Chiba, Japan.
LA  - eng
GR  - Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and 
      Technology of Japan/
GR  - Nihon University Multidisciplinary Research Grant for 2018/
PT  - Journal Article
DEP - 20210228
PL  - United States
TA  - J Periodontal Res
JT  - Journal of periodontal research
JID - 0055107
RN  - 0 (Gsdmd protein, mouse)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphate-Binding Proteins)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - Caspase 1
MH  - Cells, Cultured
MH  - *Inflammasomes
MH  - Inflammation
MH  - Interleukin-1beta
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mice
MH  - Phosphate-Binding Proteins
MH  - *Pyroptosis
OTO - NOTNLM
OT  - P. gingivalis
OT  - Dec2
OT  - Pyroptosis
OT  - periodontal inflammation
EDAT- 2021/03/01 06:00
MHDA- 2021/05/19 06:00
CRDT- 2021/02/28 20:41
PHST- 2020/12/14 00:00 [revised]
PHST- 2020/09/15 00:00 [received]
PHST- 2020/12/30 00:00 [accepted]
PHST- 2021/03/01 06:00 [pubmed]
PHST- 2021/05/19 06:00 [medline]
PHST- 2021/02/28 20:41 [entrez]
AID - 10.1111/jre.12849 [doi]
PST - ppublish
SO  - J Periodontal Res. 2021 Jun;56(3):492-500. doi: 10.1111/jre.12849. Epub 2021 Feb 
      28.