PMID- 29413962
OWN - NLM
STAT- MEDLINE
DCOM- 20181011
LR  - 20211204
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 15
DP  - 2018 May
TI  - Homocysteine causes dysfunction of chondrocytes and oxidative stress through 
      repression of SIRT1/AMPK pathway: A possible link between hyperhomocysteinemia 
      and osteoarthritis.
PG  - 504-512
LID - S2213-2317(18)30037-5 [pii]
LID - 10.1016/j.redox.2018.01.010 [doi]
AB  - Emerging evidence has indicated that the perturbed expression of homocysteine 
      (Hcy) may induce mitochondrial dysfunction and disturb bone metabolism. Sirtuin 1 
      (SIRT1) and AMP-activated protein kinase (AMPK) are two critical sensors that 
      regulate mitochondrial biogenesis and have been recognized as therapeutic targets 
      in osteoarthritis (OA). This study was designed to test whether Hcy caused 
      pro-osteoarthritic changes through modulation of SIRT1 and AMPK. Our results 
      showed that administration of Hcy reduced the SIRT1/AMPK/PGC-1alpha signaling in 
      chondrocytes, leading to mitochondrial dysfunction as a result of increased 
      oxidative stress and apoptosis. Moreover, we demonstrated that the expression of 
      NF-kappaB, COX-2, IL-8, and MMP-13 were elevated subsequent to inhibition of 
      SIRT1/AMPK/PGC-1alpha/PPAR-gamma pathway by homocysteine, thereby causing detrimental 
      effects on chondrocytes. In the animal model of diet-induced hyperhomocysteinemia 
      (HHcy), we observed the similar findings that SIRT1/PGC-1alpha/PPAR-gamma cascades were 
      downregulated with elevated MMP-13 and COX-2. Taken together, data from the 
      current study revealed that the reduced SIRT1 by Hcy may contribute to 
      degradative cartilage process, which provided insight into the etiology of OA.
CI  - Copyright (c) 2018. Published by Elsevier B.V.
FAU - Ma, Ching-Hou
AU  - Ma CH
AD  - Department of Orthopedics, E-Da hospital/I-Shou University, Kaohsiung, Taiwan.
FAU - Chiua, Yen Chun
AU  - Chiua YC
AD  - Department of Orthopedics, E-Da Cancer Hospital, Taiwan.
FAU - Wu, Chin-Hsien
AU  - Wu CH
AD  - Department of Orthopedics, E-Da hospital/I-Shou University, Kaohsiung, Taiwan.
FAU - Jou, I-Ming
AU  - Jou IM
AD  - Department of Orthopedics, E-Da hospital/I-Shou University, Kaohsiung, Taiwan.
FAU - Tu, Yuan-Kun
AU  - Tu YK
AD  - Department of Orthopedics, E-Da hospital/I-Shou University, Kaohsiung, Taiwan.
FAU - Hung, Ching-Hsia
AU  - Hung CH
AD  - Department of Physical Therapy, College of Medicine, National Cheng Kung 
      University, Tainan, Taiwan; Institute of Allied Health Sciences, College of 
      Medicine, National Cheng Kung University, Tainan, Taiwan.
FAU - Hsieh, Pei-Ling
AU  - Hsieh PL
AD  - Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan. 
      Electronic address: akinosha@hotmail.com.
FAU - Tsai, Kun-Ling
AU  - Tsai KL
AD  - Department of Physical Therapy, College of Medicine, National Cheng Kung 
      University, Tainan, Taiwan. Electronic address: kunlingtsai@mail.ncku.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180203
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (PPAR gamma)
RN  - 0 (PPARGC1A protein, human)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Animals
MH  - Chondrocytes/metabolism/pathology
MH  - Cyclooxygenase 2/genetics
MH  - Gene Expression Regulation/drug effects
MH  - Homocysteine/administration & dosage
MH  - Humans
MH  - Hyperhomocysteinemia/complications/drug therapy/*genetics/metabolism
MH  - Matrix Metalloproteinase 13/genetics
MH  - Mice
MH  - Mitochondria/genetics/pathology
MH  - Osteoarthritis/complications/drug therapy/*genetics/metabolism
MH  - Oxidative Stress/*genetics
MH  - PPAR gamma/genetics
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/*genetics
MH  - Protein Kinases/*genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirtuin 1/*genetics/metabolism
PMC - PMC5881416
OTO - NOTNLM
OT  - AMPK
OT  - Chondrocytes
OT  - Hyperhomocysteinemia
OT  - Osteoarthritis
OT  - SIRT1
EDAT- 2018/02/08 06:00
MHDA- 2018/10/12 06:00
PMCR- 2018/02/03
CRDT- 2018/02/08 06:00
PHST- 2018/01/17 00:00 [received]
PHST- 2018/01/20 00:00 [revised]
PHST- 2018/01/22 00:00 [accepted]
PHST- 2018/02/08 06:00 [pubmed]
PHST- 2018/10/12 06:00 [medline]
PHST- 2018/02/08 06:00 [entrez]
PHST- 2018/02/03 00:00 [pmc-release]
AID - S2213-2317(18)30037-5 [pii]
AID - 10.1016/j.redox.2018.01.010 [doi]
PST - ppublish
SO  - Redox Biol. 2018 May;15:504-512. doi: 10.1016/j.redox.2018.01.010. Epub 2018 Feb 
      3.