PMID- 33840739
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20220531
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 134
IP  - 8
DP  - 2021 Apr 8
TI  - Effects of HDAC4 on IL-1beta-induced matrix metalloproteinase expression regulated 
      partially through the WNT3A/beta-catenin pathway.
PG  - 963-970
LID - 10.1097/CM9.0000000000001470 [doi]
AB  - BACKGROUND: Histone deacetylase 4 (HDAC4) regulates chondrocyte hypertrophy and 
      bone formation. The aim of the present study was to explore the effects of HDAC4 
      on Interleukin 1 beta (IL-1beta)-induced chondrocyte extracellular matrix 
      degradation and whether it is regulated through the WNT family member 3A 
      (WNT3A)/beta-catenin signaling pathway. METHODS: Primary chondrocytes (CC) and human 
      chondrosarcoma cells (SW1353 cells) were treated with IL-1beta and the level of 
      HDAC4 was assayed using Western blotting. Then, HDAC4 expression in the SW1353 
      cells was silenced using small interfering RNA to detect the effect of HDAC4 
      knockdown on the levels of matrix metalloproteinase 3 (MMP3) and MMP13 induced by 
      IL-1beta. After transfection with HDAC4 plasmids, the overexpression efficiency was 
      examined using Real-time quantitative polymerase chain reaction (qRT-PCR) and the 
      levels of MMP3 and MMP13 were assayed using Western blotting. After incubation 
      with IL-1beta, the translocation of beta-catenin into the nucleus was observed using 
      immunofluorescence staining in SW1353 cells to investigate the activation of the 
      WNT3A/beta-catenin signaling pathway. Finally, treatment with WNT3A and transfection 
      with glycogen synthase kinase 3 beta (GSK3beta) plasmids were assessed for their 
      effects on HDAC4 levels using Western blotting. RESULTS: IL-1beta downregulated 
      HDAC4 levels in chondrocytes and SW1353 cells. Furthermore, HDAC4 knockdown 
      increased the levels of MMP3 and MMP13, which contributed to the degradation of 
      the extracellular matrix. Overexpression of HDAC4 inhibited IL-1beta-induced 
      increases in MMP3 and MMP13. IL-1beta upregulated the levels of WNT3A, and WNT3A 
      reduced HDAC4 levels in SW1353 cells. GSK-3beta rescued IL-1beta-induced downregulation 
      of HDAC4 in SW1353 cells. CONCLUSION: HDAC4 exerted an inhibitory effect on 
      IL-1beta-induced extracellular matrix degradation and was regulated partially by the 
      WNT3A/beta-catenin signaling pathway.
CI  - Copyright (c) 2021 The Chinese Medical Association, produced by Wolters Kluwer, 
      Inc. under the CC-BY-NC-ND license.
FAU - Ning, Qi
AU  - Ning Q
AD  - Department of Oral and Maxillofacial Surgery, Peking University School and 
      Hospital of Stomatology, Beijing 100081, China.
FAU - Gan, Ye-Hua
AU  - Gan YH
AD  - Central Laboratory, Peking University School and Hospital of Stomatology, Beijing 
      100081, China.
FAU - Shi, Rui-Rui
AU  - Shi RR
AD  - Central Laboratory, Peking University School and Hospital of Stomatology, Beijing 
      100081, China.
FAU - Meng, Juan-Hong
AU  - Meng JH
AD  - Department of Oral and Maxillofacial Surgery, Peking University School and 
      Hospital of Stomatology, Beijing 100081, China.
LA  - eng
PT  - Journal Article
DEP - 20210408
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Interleukin-1beta)
RN  - 0 (Repressor Proteins)
RN  - 0 (WNT3A protein, human)
RN  - 0 (Wnt3A Protein)
RN  - 0 (beta Catenin)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 3.4.24.- (MMP13 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.5.1.98 (HDAC4 protein, human)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - *Chondrocytes/metabolism
MH  - Glycogen Synthase Kinase 3 beta/genetics
MH  - *Histone Deacetylases/genetics
MH  - Humans
MH  - Interleukin-1beta/pharmacology
MH  - Matrix Metalloproteinase 13/metabolism
MH  - Matrix Metalloproteinase 3
MH  - Repressor Proteins
MH  - *Wnt Signaling Pathway
MH  - Wnt3A Protein/genetics
MH  - *beta Catenin/genetics/metabolism
PMC - PMC8078302
COIS- None
EDAT- 2021/04/13 06:00
MHDA- 2021/05/15 06:00
PMCR- 2021/04/20
CRDT- 2021/04/12 06:09
PHST- 2021/04/13 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2021/04/12 06:09 [entrez]
PHST- 2021/04/20 00:00 [pmc-release]
AID - 00029330-202104200-00013 [pii]
AID - CMJ-2020-3873 [pii]
AID - 10.1097/CM9.0000000000001470 [doi]
PST - epublish
SO  - Chin Med J (Engl). 2021 Apr 8;134(8):963-970. doi: 10.1097/CM9.0000000000001470.