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Link N is Cleaved by Human Annulus Fibrosus Cells Generating a Fragment With Retained Biological Activity

Gawri, Rahul; Ouellet, Jean; Onnerfjord, Patrik; Alkhatib, Bashar; Steffen, Thomas; Heinegård, Dick LU ; Roughley, Peter; Antoniou, John; Mwale, Fackson and Haglund, Lisbet (2014) In Journal of Orthopaedic Research 32(9). p.1189-1197
Abstract
Presently, there are no established treatments to prevent, stop or even retard back pain arising from disc degeneration. Previous studies have shown that Link N can act as a growth factor and stimulate the synthesis of proteoglycans and collagens, in IVD. However, the sequences in Link N involved in modulating cellular activity are not well understood. To determine if disc cells can proteolytically process Link N, human disc cells were exposed to native Link N over a 48 h period and mass spectrometric analysis revealed that a peptide spanning residues 1-8 was generated in the presence of AF cells but not NP cells. Link N 1-8 significantly induced proteoglycan production in the presence of IL-1 beta NP and AF cells, confirming that the... (More)
Presently, there are no established treatments to prevent, stop or even retard back pain arising from disc degeneration. Previous studies have shown that Link N can act as a growth factor and stimulate the synthesis of proteoglycans and collagens, in IVD. However, the sequences in Link N involved in modulating cellular activity are not well understood. To determine if disc cells can proteolytically process Link N, human disc cells were exposed to native Link N over a 48 h period and mass spectrometric analysis revealed that a peptide spanning residues 1-8 was generated in the presence of AF cells but not NP cells. Link N 1-8 significantly induced proteoglycan production in the presence of IL-1 beta NP and AF cells, confirming that the biological effect is maintained in the first 8 amino acids of the peptide and indicating that the effect is sustained in an inflammatory environment. Thus Link-N 1-8 could be a promising candidate for biologically induced disc repair, and the identification of such a stable specific peptide may facilitate the design of compounds to promote disc repair and provide alternatives to surgical intervention for early stage disc degeneration. (C) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
IVD degeneration and regeneration, Link N, organ culture, biological, repair
in
Journal of Orthopaedic Research
volume
32
issue
9
pages
1189 - 1197
publisher
John Wiley & Sons
external identifiers
  • wos:000340587200015
  • scopus:84904422404
ISSN
1554-527X
DOI
10.1002/jor.22653
language
English
LU publication?
yes
id
823f4553-7d74-4b21-b6ba-cf922ebfbf0a (old id 4648925)
date added to LUP
2014-10-01 07:27:15
date last changed
2017-11-19 03:22:02
@article{823f4553-7d74-4b21-b6ba-cf922ebfbf0a,
  abstract     = {Presently, there are no established treatments to prevent, stop or even retard back pain arising from disc degeneration. Previous studies have shown that Link N can act as a growth factor and stimulate the synthesis of proteoglycans and collagens, in IVD. However, the sequences in Link N involved in modulating cellular activity are not well understood. To determine if disc cells can proteolytically process Link N, human disc cells were exposed to native Link N over a 48 h period and mass spectrometric analysis revealed that a peptide spanning residues 1-8 was generated in the presence of AF cells but not NP cells. Link N 1-8 significantly induced proteoglycan production in the presence of IL-1 beta NP and AF cells, confirming that the biological effect is maintained in the first 8 amino acids of the peptide and indicating that the effect is sustained in an inflammatory environment. Thus Link-N 1-8 could be a promising candidate for biologically induced disc repair, and the identification of such a stable specific peptide may facilitate the design of compounds to promote disc repair and provide alternatives to surgical intervention for early stage disc degeneration. (C) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.},
  author       = {Gawri, Rahul and Ouellet, Jean and Onnerfjord, Patrik and Alkhatib, Bashar and Steffen, Thomas and Heinegård, Dick and Roughley, Peter and Antoniou, John and Mwale, Fackson and Haglund, Lisbet},
  issn         = {1554-527X},
  keyword      = {IVD degeneration and regeneration,Link N,organ culture,biological,repair},
  language     = {eng},
  number       = {9},
  pages        = {1189--1197},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Orthopaedic Research},
  title        = {Link N is Cleaved by Human Annulus Fibrosus Cells Generating a Fragment With Retained Biological Activity},
  url          = {http://dx.doi.org/10.1002/jor.22653},
  volume       = {32},
  year         = {2014},
}