PMID- 26075533
OWN - NLM
STAT- MEDLINE
DCOM- 20160908
LR  - 20151201
IS  - 1607-8438 (Electronic)
IS  - 0300-8207 (Linking)
VI  - 56
IP  - 6
DP  - 2015 Nov
TI  - TGF-beta1 antagonizes TNF-alpha induced up-regulation of matrix metalloproteinase 3 in 
      nucleus pulposus cells: role of the ERK1/2 pathway.
PG  - 461-8
LID - 10.3109/03008207.2015.1054030 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been shown to have a catabolic effect on 
      intervertebral disc degeneration (IVDD), including increasing MMP3 expression and 
      subsequent extracellular matrix (ECM) degradation. In contrast, transforming 
      growth factor-beta1 (TGF-beta1) has an anabolic effect on nucleus pulposus (NP) cells. 
      However, the anti-catabolic effect of TGF-beta1 under inflammatory condition is 
      unknown. The aim of this study was to demonstrate whether TGF-beta1 can reverse 
      TNF-alpha-induced MMP3 increase in NP cells and to further investigate the underlying 
      mechanisms. The transcriptional activity, gene expression, and protein levels of 
      MMP3 were measured by luciferase reporter assay, qRT-PCR and western blot, 
      respectively. TNF-alpha increased MMP3 expression in rat NP cells time and dose 
      dependently. TGF-beta1 could abolish TNF-alpha-mediated up-regulation of collagen I and 
      MMP3 expression, and down-regulate aggrecan and collagen II expression. The 
      ERK1/2 signaling pathway was activated after exposure to TGF-beta1. Treatment with 
      ERK1/2 inhibitors (PD98059 and U0126) abolished the antagonistic effect of TGF-beta1 
      on TNF-alpha mediated catabolic responses. These findings provide novel evidence 
      supporting the anti-catabolic role of TGF-beta1 in IVDD, which is important for the 
      potential clinical application of TGF-beta1 in disc degenerative disorders.
FAU - Yang, Hao
AU  - Yang H
AD  - a Department of Spine Surgery , Beijing Jishuitan Hospital, Peking University , 
      Xinjiekou Dongjie , Beijing , China .
AD  - b Department of Spine Surgery , The First Affiliated Hospital of Sun Yat-sen 
      University , Guangzhou , China .
FAU - Gao, Fei
AU  - Gao F
AD  - c Department of Orthopaedic Surgery , Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology , Wuhan , China , and.
FAU - Li, Xiang
AU  - Li X
AD  - d Department of Orthopaedics , The First People's Hospital of Taizhou , Taizhou , 
      China.
FAU - Wang, Jianru
AU  - Wang J
AD  - b Department of Spine Surgery , The First Affiliated Hospital of Sun Yat-sen 
      University , Guangzhou , China .
FAU - Liu, Hui
AU  - Liu H
AD  - b Department of Spine Surgery , The First Affiliated Hospital of Sun Yat-sen 
      University , Guangzhou , China .
FAU - Zheng, Zhaomin
AU  - Zheng Z
AD  - b Department of Spine Surgery , The First Affiliated Hospital of Sun Yat-sen 
      University , Guangzhou , China .
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150729
PL  - England
TA  - Connect Tissue Res
JT  - Connective tissue research
JID - 0365263
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - *Gene Expression Regulation, Enzymologic
MH  - Intervertebral Disc Degeneration/*metabolism/pathology
MH  - Lumbar Vertebrae/*metabolism
MH  - *MAP Kinase Signaling System
MH  - Matrix Metalloproteinase 3/*biosynthesis
MH  - Mitogen-Activated Protein Kinase 3/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Transforming Growth Factor beta1/*metabolism/pharmacology
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
MH  - *Up-Regulation
OTO - NOTNLM
OT  - ERK1/2 signaling pathway
OT  - intervertebral disc degeneration
OT  - matrix metalloproteinases
OT  - transforming growth factor-beta1
OT  - tumor necrosis factor-alpha
EDAT- 2015/06/16 06:00
MHDA- 2016/09/09 06:00
CRDT- 2015/06/16 06:00
PHST- 2015/06/16 06:00 [entrez]
PHST- 2015/06/16 06:00 [pubmed]
PHST- 2016/09/09 06:00 [medline]
AID - 10.3109/03008207.2015.1054030 [doi]
PST - ppublish
SO  - Connect Tissue Res. 2015 Nov;56(6):461-8. doi: 10.3109/03008207.2015.1054030. 
      Epub 2015 Jul 29.