PMID- 32896601
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20210618
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 160
DP  - 2020 Nov 20
TI  - Homocysteine induces oxidative stress and ferroptosis of nucleus pulposus via 
      enhancing methylation of GPX4.
PG  - 552-565
LID - S0891-5849(20)31236-3 [pii]
LID - 10.1016/j.freeradbiomed.2020.08.029 [doi]
AB  - Homocysteine (Hcy) is an amino acid involved in gene methylation. Plasma 
      concentration of Hcy is elevated in the pathological condition 
      hyperhomocysteinemia (HHcy), which increases the risk of disorders of the 
      vascular, nervous and musculoskeletal systems, including chondrocyte dysfunction. 
      The present study aimed to explore the role of Hcy in intervertebral disc 
      degeneration (IVDD), using a range of techniques. A clinical epidemiological 
      study showed that HHcy is an independent risk factor for human IVDD. Cell culture 
      using rat nucleus pulposus cells showed that Hcy promotes a degenerative cell 
      phenotype (involving increased oxidative stress and cell death by ferroptosis) 
      which is mediated by upregulated methylation of GPX4. An in-vivo mouse 'puncture' 
      model of IVDD showed that folic acid (which is used to treat HHcy in humans) 
      reduced the ability of diet-induced HHcy to promote IVDD. We conclude that Hcy 
      upregulates oxidative stress and ferroptosis in the nucleus pulposus via 
      enhancing GPX4 methylation, and is a new contributing factor in IVDD.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Zhang, Xuyang
AU  - Zhang X
AD  - Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, No. 3, Qingchun Road East, Hangzhou, 310016, PR China; Key 
      Laboratory of Musculoskeletal System Degeneration and Regeneration Translational 
      Research of Zhejiang Province, PR China. Electronic address: 
      jiurizhang@zju.edu.cn.
FAU - Huang, Zhaobo
AU  - Huang Z
AD  - Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, No. 3, Qingchun Road East, Hangzhou, 310016, PR China; Key 
      Laboratory of Musculoskeletal System Degeneration and Regeneration Translational 
      Research of Zhejiang Province, PR China. Electronic address: zjuhzb@zju.edu.cn.
FAU - Xie, Ziang
AU  - Xie Z
AD  - Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, No. 3, Qingchun Road East, Hangzhou, 310016, PR China; Key 
      Laboratory of Musculoskeletal System Degeneration and Regeneration Translational 
      Research of Zhejiang Province, PR China. Electronic address: dr_xieziang@163.com.
FAU - Chen, Yilei
AU  - Chen Y
AD  - Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, No. 3, Qingchun Road East, Hangzhou, 310016, PR China; Key 
      Laboratory of Musculoskeletal System Degeneration and Regeneration Translational 
      Research of Zhejiang Province, PR China. Electronic address: babylane@sina.com.
FAU - Zheng, Zeyu
AU  - Zheng Z
AD  - Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, No. 3, Qingchun Road East, Hangzhou, 310016, PR China; Key 
      Laboratory of Musculoskeletal System Degeneration and Regeneration Translational 
      Research of Zhejiang Province, PR China. Electronic address: 
      zeyuzheng@zju.edu.cn.
FAU - Wei, Xiao'an
AU  - Wei X
AD  - Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, No. 3, Qingchun Road East, Hangzhou, 310016, PR China; Key 
      Laboratory of Musculoskeletal System Degeneration and Regeneration Translational 
      Research of Zhejiang Province, PR China. Electronic address: 
      weixiaoan@zju.edu.cn.
FAU - Huang, Bao
AU  - Huang B
AD  - Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, No. 3, Qingchun Road East, Hangzhou, 310016, PR China; Key 
      Laboratory of Musculoskeletal System Degeneration and Regeneration Translational 
      Research of Zhejiang Province, PR China. Electronic address: huangbao@zju.edu.cn.
FAU - Shan, Zhi
AU  - Shan Z
AD  - Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, No. 3, Qingchun Road East, Hangzhou, 310016, PR China; Key 
      Laboratory of Musculoskeletal System Degeneration and Regeneration Translational 
      Research of Zhejiang Province, PR China. Electronic address: 
      shanzhi2003@live.com.
FAU - Liu, Junhui
AU  - Liu J
AD  - Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, No. 3, Qingchun Road East, Hangzhou, 310016, PR China; Key 
      Laboratory of Musculoskeletal System Degeneration and Regeneration Translational 
      Research of Zhejiang Province, PR China. Electronic address: ljhzju@zju.edu.cn.
FAU - Fan, Shunwu
AU  - Fan S
AD  - Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, No. 3, Qingchun Road East, Hangzhou, 310016, PR China; Key 
      Laboratory of Musculoskeletal System Degeneration and Regeneration Translational 
      Research of Zhejiang Province, PR China. Electronic address: 0099203@zju.edu.cn.
FAU - Chen, Jian
AU  - Chen J
AD  - Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, No. 3, Qingchun Road East, Hangzhou, 310016, PR China; Key 
      Laboratory of Musculoskeletal System Degeneration and Regeneration Translational 
      Research of Zhejiang Province, PR China. Electronic address: 
      chenjian-bio@zju.edu.cn.
FAU - Zhao, Fengdong
AU  - Zhao F
AD  - Department of Orthopaedics, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, No. 3, Qingchun Road East, Hangzhou, 310016, PR China; Key 
      Laboratory of Musculoskeletal System Degeneration and Regeneration Translational 
      Research of Zhejiang Province, PR China. Electronic address: 
      zhaofengdong@zju.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200905
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Animals
MH  - *Ferroptosis
MH  - Homocysteine/metabolism
MH  - *Hyperhomocysteinemia/metabolism
MH  - Methylation
MH  - Mice
MH  - *Nucleus Pulposus/metabolism
MH  - Oxidative Stress
MH  - Rats
OTO - NOTNLM
OT  - Ferroptosis
OT  - Homocysteine
OT  - Methylation
OT  - Nucleus pulposus
OT  - Oxidative stress
EDAT- 2020/09/09 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/09/08 08:48
PHST- 2020/05/14 00:00 [received]
PHST- 2020/08/19 00:00 [revised]
PHST- 2020/08/30 00:00 [accepted]
PHST- 2020/09/09 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/09/08 08:48 [entrez]
AID - S0891-5849(20)31236-3 [pii]
AID - 10.1016/j.freeradbiomed.2020.08.029 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2020 Nov 20;160:552-565. doi: 
      10.1016/j.freeradbiomed.2020.08.029. Epub 2020 Sep 5.