PMID- 32819559
OWN - NLM
STAT- MEDLINE
DCOM- 20210211
LR  - 20211204
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 529
IP  - 4
DP  - 2020 Sep 3
TI  - Silencing UHRF1 enhances cell autophagy to prevent articular chondrocytes from 
      apoptosis in osteoarthritis through PI3K/AKT/mTOR signaling pathway.
PG  - 1018-1024
LID - S0006-291X(20)31233-X [pii]
LID - 10.1016/j.bbrc.2020.06.032 [doi]
AB  - Osteoarthritis (OA) is a common chronic degenerative joint disease, and 
      chondrocyte apoptosis is one of most important pathological changes of OA 
      pathogenesis. Growing studies have shown that Ubiquitin-like with PHD and RING 
      finger domains 1 (UHRF1) is an important epigenetic regulatory factor that 
      regulates cell proliferation and apoptosis of various tumors, but its role in OA 
      remains ill-defined. In the present study, we found that UHRF1 expression was 
      increased in human OA cartilage tissues, compared with normal cartilage tissues. 
      Interleukin-1beta (IL-1beta), a major inflammatory cytokine that promotes cartilage 
      degradation in OA, was used to stimulate primary human chondrocytes in vitro. The 
      expression of UHRF1 was also enhanced in IL-1beta-induced chondrocytes. Moreover, 
      down-regulation of UHRF1 induced an increase on cell proliferation and autophagy, 
      and a decrease on apoptosis of chondrocytes after IL-1beta treatment. Further data 
      indicated that silencing UHRF1 attenuated the up-regulation of IL-1beta on 
      phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of 
      rapamycin (mTOR) signaling pathway in chondrocytes. Then, an activator of PI3K 
      weakened the effect of UHRF1 silencing on cell proliferation, autophagy, 
      apoptosis of IL-1beta-induced chondrocytes, and the cell autophagy special inhibitor 
      3-methyladenine (3-MA) also showed a same impact on UHRF1, hence suggesting that 
      knockdown of UHRF1 enhances cell autophagy to protect chondrocytes from apoptosis 
      in OA through PI3K/AKT/mTOR signaling pathway. In conclusion, our study suggests 
      that UHRF1 may be a potential regulator of chondrocyte apoptosis in the 
      pathogenesis of OA.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Shi, Xiaojuan
AU  - Shi X
AD  - Department of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University, Xi'an, 710032, China.
FAU - Han, Lei
AU  - Han L
AD  - Department of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University, Xi'an, 710032, China.
FAU - Sun, Tianshu
AU  - Sun T
AD  - Department of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University, Xi'an, 710032, China.
FAU - Zhang, Feng
AU  - Zhang F
AD  - Department of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University, Xi'an, 710032, China.
FAU - Ji, Shiying
AU  - Ji S
AD  - Department of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University, Xi'an, 710032, China.
FAU - Zhang, Min
AU  - Zhang M
AD  - Department of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University, Xi'an, 710032, China.
FAU - Wang, Xiaoqing
AU  - Wang X
AD  - Outpatient Department, Shaanxi Provincial People's Hospital, Xi'an, 710068, 
      China.
FAU - Yang, Weihong
AU  - Yang W
AD  - Outpatient Department，No.986 Hospital，The Forth Military Medical University, 
      Xi'an, 710054, China. Electronic address: hiredyoung@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200731
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (Interleukin-1beta)
RN  - EC 2.3.2.27 (UHRF1 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Apoptosis/drug effects
MH  - *Autophagy/drug effects
MH  - CCAAT-Enhancer-Binding Proteins/*metabolism
MH  - Cartilage, Articular/*pathology
MH  - Chondrocytes/drug effects/metabolism/*pathology
MH  - Down-Regulation/drug effects
MH  - *Gene Silencing
MH  - Humans
MH  - Interleukin-1beta/pharmacology
MH  - Osteoarthritis/*pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Ubiquitin-Protein Ligases/*metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Chondrocyte
OT  - Osteoarthritis
OT  - PI3K/AKT/mTOR pathway
OT  - UHRF1
COIS- Declaration of competing interest The authors declare no conflict of interest.
EDAT- 2020/08/21 06:00
MHDA- 2021/02/12 06:00
CRDT- 2020/08/22 06:00
PHST- 2020/05/18 00:00 [received]
PHST- 2020/06/06 00:00 [accepted]
PHST- 2020/08/22 06:00 [entrez]
PHST- 2020/08/21 06:00 [pubmed]
PHST- 2021/02/12 06:00 [medline]
AID - S0006-291X(20)31233-X [pii]
AID - 10.1016/j.bbrc.2020.06.032 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2020 Sep 3;529(4):1018-1024. doi: 
      10.1016/j.bbrc.2020.06.032. Epub 2020 Jul 31.