PMID- 25209447
OWN - NLM
STAT- MEDLINE
DCOM- 20150804
LR  - 20220318
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 16
IP  - 5
DP  - 2014 Aug 20
TI  - Expression and regulation of neurotrophic and angiogenic factors during human 
      intervertebral disc degeneration.
PG  - 416
LID - 10.1186/s13075-014-0416-1 [doi]
LID - 416
AB  - INTRODUCTION: The degenerate intervertebral disc (IVD) becomes innervated by 
      sensory nerve fibres, and vascularised by blood vessels. This study aimed to 
      identify neurotrophins, neuropeptides and angiogenic factors within native IVD 
      tissue and to further investigate whether pro-inflammatory cytokines are involved 
      in the regulation of expression levels within nucleus pulposus (NP) cells, nerve 
      and endothelial cells. METHODS: Quantitative real-time PCR (qRT-PCR) was 
      performed on 53 human IVDs from 52 individuals to investigate native gene 
      expression of neurotrophic factors and their receptors, neuropeptides and 
      angiogenic factors. The regulation of these factors by cytokines was investigated 
      in NP cells in alginate culture, and nerve and endothelial cells in monolayer 
      using RT-PCR and substance P (SP) protein expression in interleukin-1 (IL-1beta) 
      stimulated NP cells. RESULTS: Initial investigation on uncultured NP cells 
      identified expression of all neurotrophins by native NP cells, whilst the nerve 
      growth factor (NGF) receptor was only identified in severely degenerate and 
      infiltrated discs, and brain derived neurotrophic factor (BDNF) receptor 
      expressed by more degenerate discs. BDNF expression was significantly increased 
      in infiltrated and degenerate samples. SP and vascular endothelial growth factor 
      (VEGF) were higher in infiltrated samples. In vitro stimulation by IL-1beta induced 
      NGF in NP cells. Neurotropin-3 was induced by tumour necrosis factor alpha in 
      human dermal microvascular endothelial cells (HDMECs). SP gene and protein 
      expression was increased in NP cells by IL-1beta. Calcitonin gene related peptide 
      was increased in SH-SY5Y cells upon cytokine stimulation. VEGF was induced by 
      IL-1beta and interleukin-6 in NP cells, whilst pleiotrophin was decreased by IL-1beta. 
      VEGF and pleiotrophin were expressed by SH-SY5Y cells, and VEGF by HDMECs, but 
      were not modulated by cytokines. CONCLUSIONS: The release of cytokines, in 
      particular IL-1beta during IVD degeneration, induced significant increases in NGF 
      and VEGF which could promote neuronal and vascular ingrowth. SP which is released 
      into the matrix could potentially up regulate the production of matrix degrading 
      enzymes and also sensitise nerves, resulting in nociceptive transmission and 
      chronic low back pain. This suggests that IL-1beta is a key regulatory cytokine, 
      involved in the up regulation of factors involved in innervation and 
      vascularisation of tissues.
FAU - Binch, Abbie L A
AU  - Binch AL
FAU - Cole, Ashley A
AU  - Cole AA
FAU - Breakwell, Lee M
AU  - Breakwell LM
FAU - Michael, Anthony L R
AU  - Michael AL
FAU - Chiverton, Neil
AU  - Chiverton N
FAU - Cross, Alison K
AU  - Cross AK
FAU - Le Maitre, Christine L
AU  - Le Maitre CL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140820
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Angiogenesis Inducing Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 134034-50-7 (pleiotrophin)
RN  - 33507-63-0 (Substance P)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inducing Agents/*metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - Calcitonin Gene-Related Peptide/genetics
MH  - Carrier Proteins/genetics
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Cytokines/genetics/metabolism/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Intervertebral Disc/*metabolism/pathology
MH  - Intervertebral Disc Degeneration/*genetics/metabolism
MH  - Middle Aged
MH  - Nerve Growth Factor/genetics
MH  - Nerve Growth Factors/*genetics
MH  - Receptors, Nerve Growth Factor/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Substance P/genetics
MH  - Vascular Endothelial Growth Factor A/genetics
MH  - Young Adult
PMC - PMC4177417
EDAT- 2014/09/12 06:00
MHDA- 2015/08/05 06:00
PMCR- 2014/08/20
CRDT- 2014/09/12 06:00
PHST- 2014/04/16 00:00 [received]
PHST- 2014/08/01 00:00 [accepted]
PHST- 2014/09/12 06:00 [entrez]
PHST- 2014/09/12 06:00 [pubmed]
PHST- 2015/08/05 06:00 [medline]
PHST- 2014/08/20 00:00 [pmc-release]
AID - s13075-014-0416-1 [pii]
AID - 416 [pii]
AID - 10.1186/s13075-014-0416-1 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2014 Aug 20;16(5):416. doi: 10.1186/s13075-014-0416-1.