PMID- 31475206
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220410
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 7
IP  - 14
DP  - 2019 Jul
TI  - Estrogen prevents articular cartilage destruction in a mouse model of AMPK 
      deficiency via ERK-mTOR pathway.
PG  - 336
LID - 10.21037/atm.2019.06.77 [doi]
LID - 336
AB  - BACKGROUND: To investigate the mechanism underlying the chondroprotective effect 
      of estrogen in AMP-activated protein kinase (AMPK) deficiency mice. METHODS: 
      Female cartilage-specific AMPKalpha double knockout (AMPKalpha cDKO) mice were generated 
      and subjected to ovariectomy (OVX). The model of osteoarthritis (OA) was induced 
      by destabilization of medial meniscus (DMM). Histopathological changes were 
      evaluated by using OARSI scoring systems. Autophagy changes were analyzed by 
      immunofluorescence staining. Human chondrocytes were subjected to mechanical 
      stress to mimic OA development. and incubated in presence of or absence of 
      17beta-estradiol or/and compound C (AMPK inhibitor) or/and U0126 (ERK inhibitor). 
      The expression levels of ERK1/2 phosphorylation, p70S6K phosphorylation and light 
      chain 3 (LC3) were detected by Western blot. RESULTS: Compared with in OVX-sham 
      AMPKalpha cDKO and OVX-sham WT mice, DMM-induced OA is more severe, and significantly 
      low level of LC3 was observed in articular cartilage in OVX AMPK cDKO mice. Both 
      mechanical stress and compound C were shown to induce an increase in 
      phosphorylation of p70S6K, respectively. 17beta-estradiol stimulation led to a 
      reduction in the basal level of p70S6K phosphorylation as well as in the compound 
      C or mechanical stress-induced level of p70S6K phosphorylation. 17beta-estradiol 
      stimulation not only led to an increase in LC3 conversion but also overrode the 
      inhibitory effect of compound C on LC3 conversion. The effects of 17beta-estradiol 
      were abrogated by blocking ERK signaling pathway. CONCLUSIONS: Our findings 
      suggest that estrogen can protect articular cartilage from damage during OA 
      development by promoting chondrocyte autophagy via ERK-mammalian target of 
      rapamycin (mTOR) signaling, and give new insight into the mechanism of the 
      chondroprotective effect of estrogen.
FAU - Ge, Yuxiang
AU  - Ge Y
AD  - Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower 
      Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, China.
FAU - Zhou, Sheng
AU  - Zhou S
AD  - Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower 
      Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, China.
FAU - Li, Yixuan
AU  - Li Y
AD  - Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower 
      Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, China.
FAU - Wang, Zixu
AU  - Wang Z
AD  - Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower 
      Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, China.
FAU - Chen, Shuai
AU  - Chen S
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, China.
FAU - Xia, Tianwei
AU  - Xia T
AD  - Department of Traumatology and Orthopedics, Jiangsu Traditional Chinese Medicine 
      Hospital, Nanjing 210029, China.
FAU - Shen, Jirong
AU  - Shen J
AD  - Department of Traumatology and Orthopedics, Jiangsu Traditional Chinese Medicine 
      Hospital, Nanjing 210029, China.
FAU - Teng, Huajian
AU  - Teng H
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, China.
FAU - Jiang, Qing
AU  - Jiang Q
AD  - Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower 
      Hospital, School of Medicine, Nanjing University, Nanjing 210008, China.
AD  - Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), 
      Nanjing University, Nanjing 210093, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC6694256
OTO - NOTNLM
OT  - AMP-activated protein kinase (AMPK)
OT  - Estrogen
OT  - chondrocytes
OT  - mammalian target of rapamycin (mTOR)
OT  - osteoarthritis (OA)
COIS- Conflicts of Interest: The authors have no conflicts of interest to declare.
EDAT- 2019/09/03 06:00
MHDA- 2019/09/03 06:01
PMCR- 2019/07/01
CRDT- 2019/09/03 06:00
PHST- 2019/09/03 06:00 [entrez]
PHST- 2019/09/03 06:00 [pubmed]
PHST- 2019/09/03 06:01 [medline]
PHST- 2019/07/01 00:00 [pmc-release]
AID - atm-07-14-336 [pii]
AID - 10.21037/atm.2019.06.77 [doi]
PST - ppublish
SO  - Ann Transl Med. 2019 Jul;7(14):336. doi: 10.21037/atm.2019.06.77.