PMID- 25062286
OWN - NLM
STAT- MEDLINE
DCOM- 20141203
LR  - 20211203
IS  - 1547-5646 (Electronic)
IS  - 1547-5646 (Linking)
VI  - 21
IP  - 4
DP  - 2014 Oct
TI  - Nerve growth factor promotes expression of novel genes in intervertebral disc 
      cells that regulate tissue degradation: Laboratory investigation.
PG  - 653-61
LID - 10.3171/2014.6.SPINE13756 [doi]
AB  - OBJECT: Increased neurotrophin activity in degenerative intervertebral discs 
      (IVDs) is one potential cause of chronic low-back pain (LBP). The aim of the 
      study was to assess if nerve growth factor (NGF) might alter gene expression of 
      IVD cells and contribute to disc degeneration by enhancing expression or activity 
      of factors that cause breakdown of IVD matrix. METHODS: Rat-tail IVD cells were 
      stimulated by NGF and subjected to microarray analysis. Real-time polymerase 
      chain reaction, Western blotting, and immunocytochemistry of rat and human IVD 
      cells and tissues treated with NGF in vitro in the absence or presence of the NGF 
      inhibitor Ro 08-2750 were used to confirm findings of the microarray studies. 
      Phosphorylation of mitogen-activated protein kinase (MAPK) was used to identify 
      cell signaling pathways involved in NGF stimulation in the absence or presence of 
      Ro 08-2750. RESULTS: Microarray analysis demonstrated increased expression of 
      chitinase 3-like 1 (Chi3l1), lipocalin 2 (Lcn2), and matrix metalloproteinase-3 
      (Mmp3) following NGF stimulation of rat IVD cells in vitro. Increased gene 
      expression was confirmed by real-time polymerase chain reaction with a relative 
      increase in the Mmp/Timp ratio. Increased expression of Chi3l1, Lcn2, and Mmp3 
      following NGF stimulation was also demonstrated in rat cells and human tissue in 
      vitro. Effects of NGF on protein expression were blocked by an NGF inhibitor and 
      appear to function through the extracellular-regulation kinase 1/2 (ERK1/2) MAPK 
      pathway. CONCLUSIONS: Nerve growth factor has potential effects on matrix 
      turnover activity and influences the catabolic/anabolic balance of IVD cells in 
      an adverse way that may potentiate IVD degeneration. Anti-NGF treatment might be 
      beneficial to ameliorate progressive tissue breakdown in IVD degeneration and may 
      lead to pain relief.
FAU - Kao, Ting-Hsien
AU  - Kao TH
AD  - Graduate Institute of Medical Science, National Defense Medical Center, and.
FAU - Peng, Yi-Jen
AU  - Peng YJ
FAU - Tsou, Hsi-Kai
AU  - Tsou HK
FAU - Salter, Donald M
AU  - Salter DM
FAU - Lee, Herng-Sheng
AU  - Lee HS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140725
PL  - United States
TA  - J Neurosurg Spine
JT  - Journal of neurosurgery. Spine
JID - 101223545
RN  - 0 (2,3,4,10-tetrahydro-7,10-dimethyl-2,4-dioxobenzo(g)pteridine)
RN  - 0 (CHI3L1 protein, rat)
RN  - 0 (Chitinase-3-Like Protein 1)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Flavins)
RN  - 0 (Glycoproteins)
RN  - 0 (Lcn2 protein, rat)
RN  - 0 (Lipocalin-2)
RN  - 0 (Lipocalins)
RN  - 0 (Pteridines)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.11.24 (Mapk1 protein, rat)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Chitinase-3-Like Protein 1
MH  - Extracellular Matrix Proteins/*genetics
MH  - Flavins
MH  - Gene Expression/*drug effects
MH  - Glycoproteins/*genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - Intervertebral Disc Degeneration/*drug therapy/genetics
MH  - Lipocalin-2
MH  - Lipocalins/*genetics
MH  - Male
MH  - Matrix Metalloproteinase 3/*genetics
MH  - Microarray Analysis
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Nerve Growth Factor/*pharmacology
MH  - Phosphorylation
MH  - Pteridines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Real-Time Polymerase Chain Reaction
OTO - NOTNLM
OT  - AF = annulus fibrosus
OT  - BSA = bovine serum albumin
OT  - Chi3l1 = chitinase 3-like 1
OT  - EPK1/2 = extracellular-regulation kinase 1/2
OT  - HRP = horseradish peroxidase
OT  - IL-1beta = interleukin-1beta
OT  - IVD = intervertebral disc
OT  - LBP = low-back pain
OT  - Lcn2 = lipocalin 2
OT  - MAPK = mitogen-activated protein kinase
OT  - MMP3
OT  - Mmp3 = matrix metalloproteinase-3
OT  - NF-kappaB = neurotrophic factor kappaB
OT  - NGF = nerve growth factor
OT  - NGFR = nerve growth factor receptor
OT  - NP = nucleus pulposus
OT  - PBS = phosphate-buffered saline
OT  - TBST = Tris-buffered saline/Tween
OT  - VE = vertebral endplate
OT  - chitinase 3-like 1
OT  - intervertebral disc degeneration
OT  - lipocalin 2
OT  - nerve growth factor
OT  - p75NTR = p75 neurotrophin receptor
EDAT- 2014/07/26 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/07/26 06:00
PHST- 2014/07/26 06:00 [entrez]
PHST- 2014/07/26 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.3171/2014.6.SPINE13756 [doi]
PST - ppublish
SO  - J Neurosurg Spine. 2014 Oct;21(4):653-61. doi: 10.3171/2014.6.SPINE13756. Epub 
      2014 Jul 25.