title: Link N is cleaved by human annulus fibrosus cells generating a fragment with retained biological activity.
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-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.
authors.affiliation: Orthopaedic Research Laboratory, Royal Victoria Hospital, McGill University, Montréal, Canada; Orthopaedic Research Laboratory, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, Canada; McGill Scoliosis and Spine Center, McGill University, Montréal, Canada; Department of Surgery, McGill University, Montréal, Canada.
authors.forename: Rahul
authors.initials: R
authors.lastname: Gawri
authors.forename: Jean
authors.initials: J
authors.lastname: Ouellet
authors.forename: Patrik
authors.initials: P
authors.lastname: Önnerfjord
authors.forename: Bashar
authors.initials: B
authors.lastname: Alkhatib
authors.forename: Thomas
authors.initials: T
authors.lastname: Steffen
authors.forename: Dick
authors.initials: D
authors.lastname: Heinegård
authors.forename: Peter
authors.initials: P
authors.lastname: Roughley
authors.forename: John
authors.initials: J
authors.lastname: Antoniou
authors.forename: Fackson
authors.initials: F
authors.lastname: Mwale
authors.forename: Lisbet
authors.initials: L
authors.lastname: Haglund
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001685:Biological Factors / Q000378:metabolism* / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000378:metabolism / Q000473:pathology; D008159:Lumbar Vertebrae / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D013904:Thoracic Vertebrae / Q000473:pathology; D055815:Young Adult
chemical_list: D001685:Biological Factors; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D011509:Proteoglycans; D003094:Collagen
keywords: IVD degeneration and regeneration; Link N; biological repair; organ culture