Neuropeptides regulate expression of matrix molecule, growth factor and inflammatory mediator mRNA in explants of normal and healing medial collateral ligament.
Denervation degrades normal ligament properties and impairs ligament healing. This suggests that secreted neuromediators, such as neuropeptides, could be modulating cell metabolism in ligament and scar tissue. To test this hypothesis we investigated the effect of exogenous substance P (SP), neuropeptide Y (NPY) or calcitonin gene-related peptide (CGRP) on the mRNA levels for proteins associated with inflammation, angiogenesis, and matrix production in tissue-cultured specimens of normal and injured medial collateral ligament. SP and NPY induced increased mRNA levels for several inflammatory mediators in the 2-week post-injury specimens. All three neuropeptides induced decreases in mRNA levels for healing-associated growth factors and matrix molecules, including basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and collagen types I and III. The results indicate that neuropeptides strongly influence the metabolic activity of cells in healing ligament, particularly at early time points after injury.
Salo
Paul
P
Department of Surgery, University of Calgary, Calgary, Alberta, Canada. salo@ucalgary.ca
Bray
Robert
R
Seerattan
Ruth
R
Reno
Carol
C
McDougall
Jason
J
Hart
David A
DA
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D017885:Collateral Ligaments / Q000187:drug effects* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D009478:Neuropeptide Y / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013373:Substance P / Q000494:pharmacology; D046509:Tissue Culture Techniques; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects*
D024042:Collagen Type I; D024061:Collagen Type III; D009478:Neuropeptide Y; D009479:Neuropeptides; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide