PMID- 23091643
OWN - NLM
STAT- MEDLINE
DCOM- 20130328
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 10
DP  - 2012
TI  - Degenerate human nucleus pulposus cells promote neurite outgrowth in neural 
      cells.
PG  - e47735
LID - 10.1371/journal.pone.0047735 [doi]
LID - e47735
AB  - Innervation of nociceptive nerve fibres into the normally aneural nucleus 
      pulposus (NP) of the intervertebral disc (IVD) occurs during degeneration 
      resulting in discogenic back pain. The neurotrophins nerve growth factor (NGF) 
      and brain-derived neurotrophic factor (BDNF), which are associated with 
      stimulation of axonal outgrowth and nociception by neuronal cells, are both 
      expressed by NP cells, with BDNF levels increasing with disease severity. However 
      the mechanism of interaction between human NP cells and neural cells has yet to 
      be fully elucidated. Therefore the aim of this study was to determine whether 
      non-degenerate or degenerate human NP cells inhibit or stimulate neural outgrowth 
      and whether any outgrowth is mediated by NGF or BDNF. Human NP cells from 
      non-degenerate and degenerate IVD were cultured in alginate beads then 
      co-cultured for 48 hours with human SH-SY5Y neuroblastoma cells. Co-culture of 
      non-degenerate NP cells with neural cells resulted in both an inhibition of 
      neurite outgrowth and reduction in percentage of neurite expressing cells. 
      Conversely co-culture with degenerate NP cells resulted in an increase in both 
      neurite length and percentage of neurite expressing cells. Addition of anti-NGF 
      to the co-culture with degenerate cells resulted in a decrease in percentage of 
      neurite expressing cells, while addition of anti-BDNF resulted in a decrease in 
      both neurite length and percentage of neurite expressing cells. Our findings show 
      that while non-degenerate NP cells are capable of inhibiting neurite outgrowth 
      from human neural cells, degenerate NP cells stimulate outgrowth. Neurotrophin 
      blocking studies demonstrated that both NGF and BDNF, secreted by degenerate NP 
      cells, may play a role in this stimulation with BDNF potentially playing the 
      predominant role. These findings suggest that NP cells are capable of regulating 
      nerve ingrowth and that neoinnervation occurring during IVD degeneration may be 
      stimulated by the NP cells themselves.
FAU - Richardson, Stephen M
AU  - Richardson SM
AD  - Centre for Regenerative Medicine, Institute of Inflammation and Repair, Faculty 
      of Medical and Human Sciences, The University of Manchester, Manchester, United 
      Kingdom.
FAU - Purmessur, Devina
AU  - Purmessur D
FAU - Baird, Pauline
AU  - Baird P
FAU - Probyn, Ben
AU  - Probyn B
FAU - Freemont, Anthony J
AU  - Freemont AJ
FAU - Hoyland, Judith A
AU  - Hoyland JA
LA  - eng
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121016
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Alginates)
RN  - 0 (Hexuronic Acids)
RN  - 8A5D83Q4RW (Glucuronic Acid)
SB  - IM
MH  - Alginates
MH  - Cell Line
MH  - Coculture Techniques
MH  - Glucuronic Acid
MH  - Hexuronic Acids
MH  - Humans
MH  - Intervertebral Disc/cytology/*metabolism
MH  - Intervertebral Disc Degeneration/*metabolism/pathology
MH  - Neurites/*metabolism
PMC - PMC3472988
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/10/24 06:00
MHDA- 2013/03/30 06:00
PMCR- 2012/10/16
CRDT- 2012/10/24 06:00
PHST- 2012/08/01 00:00 [received]
PHST- 2012/09/14 00:00 [accepted]
PHST- 2012/10/24 06:00 [entrez]
PHST- 2012/10/24 06:00 [pubmed]
PHST- 2013/03/30 06:00 [medline]
PHST- 2012/10/16 00:00 [pmc-release]
AID - PONE-D-12-22804 [pii]
AID - 10.1371/journal.pone.0047735 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(10):e47735. doi: 10.1371/journal.pone.0047735. Epub 2012 Oct 16.