PMID- 32805694
OWN - NLM
STAT- MEDLINE
DCOM- 20210331
LR  - 20210331
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 88
DP  - 2020 Nov
TI  - Inhibition of GPR17 with pranlukast protects against TNF-alpha-induced loss of type 
      II collagen in ATDC5 cells.
PG  - 106870
LID - S1567-5769(20)30864-X [pii]
LID - 10.1016/j.intimp.2020.106870 [doi]
AB  - Osteoarthritis (OA) is a common joint disease affecting millions of elderly 
      people worldwide. However, the mechanism of OA is complicated and remains poorly 
      understood. Thus, a safe and effective therapeutic strategy has yet to be 
      developed. G protein-coupled receptor 17 (GPR17) is an orphan receptor that is 
      widely distributed in the central nervous system (CNS). GPR17 has become a target 
      for the treatment of inflammation in brain diseases. In this study, we 
      demonstrate that GPR17 is expressed in ATDC5 cells and is increased in response 
      to TNF-alpha exposure. We also found that antagonism of GPR17 with pranlukast 
      significantly inhibited oxidative stress by downregulating the intracellular 
      level of reactive oxygen species (ROS) and increasing the activity of super oxide 
      dismutase (SOD) against TNF-alpha. Interestingly, treatment with pranlukast prevented 
      TNF-alpha-induced reduction of type II collagen. Additionally, knockdown of GPR17 
      with siRNA ameliorated TNF-alpha-induced loss of type II collagen, suggesting the 
      importance of the role of GPR17 in mediating the impairment of type II collagen. 
      Blockage of GPR17 with pranlukast suppressed the expression of matrix 
      metalloproteinases 3 (MMP-3) and matrix metalloproteinases 13 (MMP-13), which 
      contribute to the degradation of type II collagen. Pranlukast also prevented the 
      activation of the JAK2/STAT1/IRF-1 signaling pathway, thereby suppressing the 
      expression of pro-inflammatory cytokines and enzymes. Furthermore, pranlukast 
      rescued TNF-alpha-induced reduced SOX-9 expression. Together, our data indicate that 
      GPR17 might be a potential target for the treatment of OA.
CI  - Copyright (c) 2020. Published by Elsevier B.V.
FAU - Wang, Zhangfu
AU  - Wang Z
AD  - Department of Spine Surgery, Taizhou Hospital of Wenzhou Medical University, 
      Linhai, Taizhou 317000, China.
FAU - Zhou, Weiwei
AU  - Zhou W
AD  - Department of Spine Surgery, Taizhou Hospital of Wenzhou Medical University, 
      Linhai, Taizhou 317000, China.
FAU - Zheng, Guangbin
AU  - Zheng G
AD  - Department of Spine Surgery, Taizhou Hospital of Wenzhou Medical University, 
      Linhai, Taizhou 317000, China.
FAU - Yang, Guangyong
AU  - Yang G
AD  - Department of Spine Surgery, Taizhou Hospital of Wenzhou Medical University, 
      Linhai, Taizhou 317000, China. Electronic address: yanggy0576@163.com.
LA  - eng
PT  - Journal Article
DEP - 20200814
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Chromones)
RN  - 0 (Collagen Type II)
RN  - 0 (GPR17 protein, mouse)
RN  - 0 (Interferon Regulatory Factor-1)
RN  - 0 (Irf1 protein, mouse)
RN  - 0 (Leukotriene Antagonists)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (SOX9 Transcription Factor)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (Sox9 protein, mouse)
RN  - 0 (Stat1 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.7.10.2 (Jak2 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.- (Mmp13 protein, mouse)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.17 (Mmp3 protein, mouse)
RN  - TB8Z891092 (pranlukast)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Chromones/*pharmacology
MH  - Collagen Type II/*drug effects/genetics/*metabolism
MH  - Gene Knockdown Techniques
MH  - Interferon Regulatory Factor-1/metabolism
MH  - Janus Kinase 2/metabolism
MH  - Leukotriene Antagonists/*pharmacology
MH  - Matrix Metalloproteinase 13/metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Mice
MH  - Nerve Tissue Proteins/*antagonists & inhibitors/genetics/*metabolism
MH  - Osteoarthritis/prevention & control
MH  - Oxidative Stress/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, G-Protein-Coupled/*antagonists & inhibitors/genetics/*metabolism
MH  - SOX9 Transcription Factor/metabolism
MH  - STAT1 Transcription Factor/metabolism
MH  - Signal Transduction/drug effects
MH  - Superoxide Dismutase/metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
OTO - NOTNLM
OT  - GPR17
OT  - IRF-1
OT  - JAK2/STAT1
OT  - MMPs
OT  - Osteoarthritis
OT  - Oxidative stress
OT  - Pranlukast
OT  - SOX-9
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/08/18 06:00
MHDA- 2021/04/01 06:00
CRDT- 2020/08/18 06:00
PHST- 2020/03/23 00:00 [received]
PHST- 2020/07/20 00:00 [revised]
PHST- 2020/07/31 00:00 [accepted]
PHST- 2020/08/18 06:00 [pubmed]
PHST- 2021/04/01 06:00 [medline]
PHST- 2020/08/18 06:00 [entrez]
AID - S1567-5769(20)30864-X [pii]
AID - 10.1016/j.intimp.2020.106870 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2020 Nov;88:106870. doi: 10.1016/j.intimp.2020.106870. Epub 
      2020 Aug 14.