PMID- 29755657
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 29
DP  - 2018 Apr 17
TI  - Regulatory effect of anti-gp130 functional mAb on IL-6 mediated RANKL and Wnt5a 
      expression through JAK-STAT3 signaling pathway in FLS.
PG  - 20366-20376
LID - 10.18632/oncotarget.23917 [doi]
AB  - We investigated the effect on rheumatoid arthritis (RA) of an anti-gp130 
      monoclonal antibody (mAb) and its mechanism using RA fibroblast-like synoviocytes 
      (FLS) and a collagen antibody-induced arthritis (CAIA) mouse model. We determined 
      the interleukin 6 (IL-6), IL-6 receptor alpha (IL-6Ralpha), gp130, receptor activator of 
      nuclear factor kappaB ligand (RANKL), matrix metalloproteinase 3 (MMP3), TIMP 
      metallopeptidase inhibitor 1 (TIMP1), and Bcl-2 levels in RA and osteoarthritis 
      (OA) serum and synovial fluid. RA FLS were cultured with or without IL-6/IL-6Ralpha; 
      WNT5A and RANKL levels were detected. We generated an anti-gp130 mAb (M10) with 
      higher affinity and specificity, blocked IL-6 signaling with it, and assessed its 
      effects on the CAIA model, WNT5A and RANKL expression, and signal transducer and 
      activator of transcription 3 (STAT3) phosphorylation. The IL-6 signaling system 
      in patients with RA was increased; RANKL, MMP3, TIMP1, and Bcl-2 in RA bone were 
      elevated. IL-6/IL-6Ralpha increased RA FLS WNT5A and RANKL expression. M10 
      ameliorated arthritis in the CAIA model, and inhibited RANKL, WNT5A, and Bcl-2 
      expression in RA FLS by blocking IL-6 signaling, likely via Janus kinase-STAT3 
      pathway downregulation. The IL-6-soluble IL-6Ralpha-gp130 complex is hyperactive in 
      RA and OA. M10 may be the basis for a novel RA treatment drug.
FAU - Miao, Ping
AU  - Miao P
AD  - Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai 
      Jiao Tong University, Shanghai, China.
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Zhou, Xiao Wei
AU  - Zhou XW
AD  - Reproductive Medical Center of Ruijin Hospital, School of Medicine, Shanghai Jiao 
      Tong University, Shanghai, China.
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Wang, Ping
AU  - Wang P
AD  - Shanghai Jiao Tong University School of Medicine, XinHua Hospital, Shanghai, 
      China.
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Zhao, Rong
AU  - Zhao R
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
AD  - Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Chen, Ninan
AU  - Chen N
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
AD  - Department of Pediatrics, Ruijin Hospital and Ruijin Hospital North, Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Hu, Chao Ying
AU  - Hu CY
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
AD  - Central laboratory, Shanghai Xuhui Central Hospital, Shanghai, China.
FAU - Chen, Xue Hua
AU  - Chen XH
AD  - Department of Pediatrics, Ruijin Hospital and Ruijin Hospital North, Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Qian, Liu
AU  - Qian L
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Yu, Qi Wen
AU  - Yu QW
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Zhang, Ji Ying
AU  - Zhang JY
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
FAU - Xu, Rong
AU  - Xu R
AD  - Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western 
      Medicine, Shanghai, China.
FAU - He, Dong Yi
AU  - He DY
AD  - Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western 
      Medicine, Shanghai, China.
FAU - Xiao, Lian Bo
AU  - Xiao LB
AD  - Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western 
      Medicine, Shanghai, China.
FAU - Li, Pu
AU  - Li P
AD  - Department of Pediatrics, Ruijin Hospital and Ruijin Hospital North, Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Lu, Mason
AU  - Lu M
AD  - MedAbome, Inc, Fremont, CA, USA.
FAU - Zhang, Dong Qing
AU  - Zhang DQ
AD  - Shanghai Institute of Immunology, Shanghai Jiao Tong University School of 
      Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20180104
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5945543
OTO - NOTNLM
OT  - STAT3
OT  - collagen II antibody-induced arthritis
OT  - gp130
OT  - receptor activator of nuclear factor kappaB ligand
OT  - rheumatoid arthritis
COIS- CONFLICTS OF INTEREST The authors declare that they have no competing interest.
EDAT- 2018/05/15 06:00
MHDA- 2018/05/15 06:01
PMCR- 2018/04/17
CRDT- 2018/05/15 06:00
PHST- 2017/09/07 00:00 [received]
PHST- 2017/12/11 00:00 [accepted]
PHST- 2018/05/15 06:00 [entrez]
PHST- 2018/05/15 06:00 [pubmed]
PHST- 2018/05/15 06:01 [medline]
PHST- 2018/04/17 00:00 [pmc-release]
AID - 23917 [pii]
AID - 10.18632/oncotarget.23917 [doi]
PST - epublish
SO  - Oncotarget. 2018 Jan 4;9(29):20366-20376. doi: 10.18632/oncotarget.23917. 
      eCollection 2018 Apr 17.