Degenerate Human Nucleus Pulposus Cells Promote Neurite Outgrowth in Neural Cells

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 s...

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Main Authors: Richardson, Stephen M., Purmessur, Devina, Baird, Pauline, Probyn, Ben, Freemont, Anthony J., Hoyland, Judith A.
Format: Online
Language:English
Published: Public Library of Science 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472988/
id pubmed-3472988
recordtype oai_dc
spelling pubmed-34729882012-10-22 Degenerate Human Nucleus Pulposus Cells Promote Neurite Outgrowth in Neural Cells Richardson, Stephen M. Purmessur, Devina Baird, Pauline Probyn, Ben Freemont, Anthony J. Hoyland, Judith A. Research Article 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. Public Library of Science 2012-10-16 /pmc/articles/PMC3472988/ /pubmed/23091643 http://dx.doi.org/10.1371/journal.pone.0047735 Text en © 2012 Richardson et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Richardson, Stephen M.
Purmessur, Devina
Baird, Pauline
Probyn, Ben
Freemont, Anthony J.
Hoyland, Judith A.
spellingShingle Richardson, Stephen M.
Purmessur, Devina
Baird, Pauline
Probyn, Ben
Freemont, Anthony J.
Hoyland, Judith A.
Degenerate Human Nucleus Pulposus Cells Promote Neurite Outgrowth in Neural Cells
author_facet Richardson, Stephen M.
Purmessur, Devina
Baird, Pauline
Probyn, Ben
Freemont, Anthony J.
Hoyland, Judith A.
author_sort Richardson, Stephen M.
title Degenerate Human Nucleus Pulposus Cells Promote Neurite Outgrowth in Neural Cells
title_short Degenerate Human Nucleus Pulposus Cells Promote Neurite Outgrowth in Neural Cells
title_full Degenerate Human Nucleus Pulposus Cells Promote Neurite Outgrowth in Neural Cells
title_fullStr Degenerate Human Nucleus Pulposus Cells Promote Neurite Outgrowth in Neural Cells
title_full_unstemmed Degenerate Human Nucleus Pulposus Cells Promote Neurite Outgrowth in Neural Cells
title_sort degenerate human nucleus pulposus cells promote neurite outgrowth in neural cells
description 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.
publisher Public Library of Science
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472988/
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