PMID- 33062145
OWN - NLM
STAT- MEDLINE
DCOM- 20210512
LR  - 20210512
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2020
DP  - 2020
TI  - Oleanolic Acid Decreases IL-1beta-Induced Activation of Fibroblast-Like Synoviocytes 
      via the SIRT3-NF-kappaB Axis in Osteoarthritis.
PG  - 7517219
LID - 10.1155/2020/7517219 [doi]
LID - 7517219
AB  - Synovial inflammation is a major pathological feature of osteoarthritis (OA), 
      which is a chronic degenerative joint disease. Fibroblast-like synoviocytes 
      (FLS), localized in the synovial membrane, are specialized secretory cells. 
      During OA synovitis, FLS produce chemokines and cytokines that stimulate 
      chondrocytes to secrete inflammatory cytokines and activate matrix 
      metalloproteinases (MMPs) in FLS. Recent studies have demonstrated that sirtuin 3 
      (SIRT3) performs as a key regulator in maintaining mitochondrial homeostasis in 
      OA. This study aims at ascertaining whether SIRT3 is involved in OA synovitis. 
      The overexpression (OE) and knockdown (KD) of SIRT3 are established by short 
      hairpin RNA (shRNA) and recombinant plasmid in human FLS. The anti-inflammatory 
      effect of SIRT3 underlying in oleanolic acid- (OLA-) prevented interleukin-1beta- 
      (IL-1beta-) induced FLS dysfunction is then evaluated in vitro. Additionally, the 
      molecular mechanisms of SIRT3 are assessed, and the interaction between SIRT3 and 
      NF-kappaB is investigated. The data suggested that SIRT3 can be detected in human 
      synovial tissues during OA, and OLA could elevate SIRT3 expression. OE-SIRT3 and 
      OLA exhibited equal authenticity to repress inflammation and reverse oxidative 
      stress changes in IL-1beta-induced human FLS dysfunction. KD-SIRT3 was found to 
      exacerbate inflammation and oxidative stress changes in human FLS. Furthermore, 
      it was found that SIRT3 could directly bind with NF-kappaB, resulting in the 
      suppression of NF-kappaB activation induced by IL-1beta in human FLS, which then 
      repressed synovial inflammation in OA. In general, the activation of SIRT3 by OLA 
      inhibited synovial inflammation by suppressing the NF-kappaB signal pathway in FLS, 
      and this suggested that SIRT3 is a potential target for OA synovitis therapy.
CI  - Copyright (c) 2020 Jiapeng Bao et al.
FAU - Bao, Jiapeng
AU  - Bao J
AD  - Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Yan, Weifeng
AU  - Yan W
AD  - Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
AD  - Department of Orthopedics, China Coast Guard Hospital of the People's Armed 
      Police Force, Jiaxing, China.
FAU - Xu, Kai
AU  - Xu K
AD  - Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Chen, Mengyao
AU  - Chen M
AD  - Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Chen, Zhonggai
AU  - Chen Z
AD  - Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Ran, Jisheng
AU  - Ran J
AD  - Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Xiong, Yan
AU  - Xiong Y
AUID- ORCID: 0000-0001-6127-2294
AD  - Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Wu, Lidong
AU  - Wu L
AUID- ORCID: 0000-0001-9057-1234
AD  - Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20200928
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Reactive Oxygen Species)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 3.5.1.- (Sirtuin 3)
SB  - IM
MH  - Aged
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cyclooxygenase 2/genetics/metabolism
MH  - Female
MH  - Humans
MH  - Interleukin-1beta/pharmacology
MH  - Male
MH  - Middle Aged
MH  - NF-kappa B/*metabolism
MH  - Oleanolic Acid/*pharmacology
MH  - Osteoarthritis/metabolism/*pathology
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Reactive Oxygen Species/chemistry/metabolism
MH  - Signal Transduction/*drug effects
MH  - Sirtuin 3/antagonists & inhibitors/genetics/*metabolism
MH  - Synoviocytes/cytology/drug effects/metabolism
MH  - Up-Regulation/drug effects
PMC - PMC7542488
COIS- All authors declare that they have no competing interests.
EDAT- 2020/10/17 06:00
MHDA- 2021/05/13 06:00
PMCR- 2020/09/28
CRDT- 2020/10/16 05:53
PHST- 2020/03/21 00:00 [received]
PHST- 2020/06/04 00:00 [revised]
PHST- 2020/08/01 00:00 [accepted]
PHST- 2020/10/16 05:53 [entrez]
PHST- 2020/10/17 06:00 [pubmed]
PHST- 2021/05/13 06:00 [medline]
PHST- 2020/09/28 00:00 [pmc-release]
AID - 10.1155/2020/7517219 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2020 Sep 28;2020:7517219. doi: 10.1155/2020/7517219. 
      eCollection 2020.