Link N is cleaved by human annulus fibrosus cells generating a fragment with retained biological activity. Gawri, R., Ouellet, J., Önnerfjord, P., Alkhatib, B., Steffen, T., Heinegård, D., Roughley, P., Antoniou, J., Mwale, F., & Haglund, L. Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society, 32(9):1189–1197, September, 2014.
doi  abstract   bibtex   
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.
@article{gawri_link_2014,
	title = {Link {N} is cleaved by human annulus fibrosus cells generating a fragment with retained biological activity},
	volume = {32},
	issn = {1554-527X},
	doi = {10.1002/jor.22653},
	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.},
	language = {eng},
	number = {9},
	journal = {Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society},
	author = {Gawri, Rahul and Ouellet, Jean and Önnerfjord, Patrik and Alkhatib, Bashar and Steffen, Thomas and Heinegård, Dick and Roughley, Peter and Antoniou, John and Mwale, Fackson and Haglund, Lisbet},
	month = sep,
	year = {2014},
	pmid = {24861010},
	keywords = {Adolescent, Adult, Amino Acid Sequence, Animals, Biological Factors, Cattle, Cells, Cultured, Collagen, Female, Humans, IVD degeneration and regeneration, Intercellular Signaling Peptides and Proteins, Intervertebral Disc, Intervertebral Disc Degeneration, Link N, Lumbar Vertebrae, Male, Middle Aged, Molecular Sequence Data, Peptide Fragments, Proteoglycans, Regeneration, Thoracic Vertebrae, Young Adult, biological repair, organ culture},
	pages = {1189--1197}
}

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