Expression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc: Association with Inflammation and Matrix Remodeling.

Détails

ID Serval
serval:BIB_66DF60A5620D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Expression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc: Association with Inflammation and Matrix Remodeling.
Périodique
International journal of molecular sciences
Auteur(s)
Kameda T., Zvick J., Vuk M., Sadowska A., Tam W.K., Leung V.Y., Bölcskei K., Helyes Z., Applegate L.A., Hausmann O.N., Klasen J., Krupkova O., Wuertz-Kozak K.
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Statut éditorial
Publié
Date de publication
10/04/2019
Peer-reviewed
Oui
Volume
20
Numéro
7
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Transient receptor potential (TRP) channels have emerged as potential sensors and transducers of inflammatory pain. The aims of this study were to investigate (1) the expression of TRP channels in intervertebral disc (IVD) cells in normal and inflammatory conditions and (2) the function of Transient receptor potential ankyrin 1 (TRPA1) and Transient receptor potential vanilloid 1 (TRPV1) in IVD inflammation and matrix homeostasis. RT-qPCR was used to analyze human fetal, healthy, and degenerated IVD tissues for the gene expression of TRPA1 and TRPV1. The primary IVD cell cultures were stimulated with either interleukin-1 beta (IL-1β) or tumor necrosis factor alpha (TNF-α) alone or in combination with TRPA1/V1 agonist allyl isothiocyanate (AITC, 3 and 10 µM), followed by analysis of calcium flux and the expression of inflammation mediators (RT-qPCR/ELISA) and matrix constituents (RT-qPCR). The matrix structure and composition in caudal motion segments from TRPA1 and TRPV1 wild-type (WT) and knock-out (KO) mice was visualized by FAST staining. Gene expression of other TRP channels (A1, C1, C3, C6, V1, V2, V4, V6, M2, M7, M8) was also tested in cytokine-treated cells. TRPA1 was expressed in fetal IVD cells, 20% of degenerated IVDs, but not in healthy mature IVDs. TRPA1 expression was not detectable in untreated cells and it increased upon cytokine treatment, while TRPV1 was expressed and concomitantly reduced. In inflamed IVD cells, 10 µM AITC activated calcium flux, induced gene expression of IL-8, and reduced disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and collagen 1A1, possibly via upregulated TRPA1. TRPA1 KO in mice was associated with signs of degeneration in the nucleus pulposus and the vertebral growth plate, whereas TRPV1 KO did not show profound changes. Cytokine treatment also affected the gene expression of TRPV2 (increase), TRPV4 (increase), and TRPC6 (decrease). TRPA1 might be expressed in developing IVD, downregulated during its maturation, and upregulated again in degenerative disc disease, participating in matrix homeostasis. However, follow-up studies with larger sample sizes are needed to fully elucidate the role of TRPA1 and other TRP channels in degenerative disc disease.
Mots-clé
Animals, Calcium Signaling, Extracellular Matrix/metabolism, Extracellular Matrix/pathology, Gene Expression Regulation, Humans, Inflammation/metabolism, Inflammation/pathology, Inflammation Mediators/metabolism, Intervertebral Disc/metabolism, Intervertebral Disc/pathology, Intervertebral Disc Degeneration/metabolism, Intervertebral Disc Degeneration/pathology, Mice, Mice, Knockout, Nucleus Pulposus/metabolism, Nucleus Pulposus/pathology, TRPA1 Cation Channel/biosynthesis, TRPV Cation Channels/biosynthesis, TRP channels, TRPA1, TRPC6, TRPV1, TRPV2, TRPV4, aggrecanases, collagen, low back pain, pro-inflammatory cytokines
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/04/2019 15:38
Dernière modification de la notice
20/08/2019 14:22
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