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Link N is cleaved by human annulus fibrosus cells generating a fragment with retained biological activity
Author(s) -
Gawri Rahul,
Ouellet Jean,
Önnerfjord Patrik,
Alkhatib Bashar,
Steffen Thomas,
Heinegård Dick,
Roughley Peter,
Antoniou John,
Mwale Fackson,
Haglund Lisbet
Publication year - 2014
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22653
Subject(s) - fragment (logic) , chemistry , annulus (botany) , microbiology and biotechnology , biophysics , biology , computer science , algorithm , botany
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‐1β 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. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1189–1197, 2014.