Effect of synthetic link N peptide on the expression of type I and type II collagens in human intervertebral disc cells.
Intervertebral disc (IVD) degeneration is associated with proteolytic degradation of proteoglycan aggregates present within the extracellular matrix of the disc. Link N peptide (DHLSDNYTLDHDRAIH) is the N-terminal peptide of link protein, which stabilizes the proteoglycan aggregates. It is generated in vivo by proteolytic degradation during tissue turnover. It has been previously shown that this peptide can stimulate the synthesis of collagens by articular cartilage and bovine IVD cells in vitro. Being a synthetic peptide, Link N has considerable financial benefits for clinical use over recombinant growth factors because it is extremely cheap to produce. The purpose of the present study was to determine the effect of Link N on the expression of types I and II collagen and investigate the cellular mechanisms of Link N signal transduction in human IVD cells. The present results suggest that Link N stimulates the expression of types I and II collagen in human IVD cells. More specifically, Link N stimulated the expression of type I in nucleus pulposus (NP) cells, but not in annulus fibrosus cells. As Link N also decreased the phosphorylation of p38 in NP cells only, results suggest that p38 is a mediator of the effect of Link N on type I collagen expression. p38 is a member of the mitogen-activated protein kinase family highlighted by three major cascades: p38, c-Jun amino-terminal kinase, and extracellular signal-regulated kinase pathways. Link N showed no effect on the latter two pathways, suggesting a specific effect of Link N on the p38 cascade. On the other hand, Link N stimulated the expression of type II collagen in both NP and annulus fibrosus, suggesting that other mechanisms are implicated in the control of type II collagen expression in disc cells, without excluding p38 for the NP. In conclusion, the present study showed that Link N can modulate the expression of collagen in human IVD cells.
Lady Davis Institute for Medical Research, SMBD-Jewish General Hospital, Montreal, QC, Canada.
Alain
A
Petit
Guoying
G
Yao
Sora Al
SA
Rowas
Rahul
R
Gawri
Laura
L
Epure
John
J
Antoniou
Fackson
F
Mwale
D024042:Collagen Type I / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology*; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011509:Proteoglycans / Q000737:chemistry*; D000099249:Proteoglycan Link Protein
D024042:Collagen Type I; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D010455:Peptides; D011509:Proteoglycans; D000099249:Proteoglycan Link Protein