TY  - JOUR
A1  - Kameda, Takuya
A1  - Zvick, Joel
A1  - Vuk, Miriam
A1  - Sadowska, Aleksandra
A1  - Tam, Wai Kit
A1  - Leung, Victor Y.
A1  - Bölcskei, Kata
A1  - Helyes, Zsuzsanna
A1  - Applegate, Lee Ann
A1  - Hausmann, Oliver N.
A1  - Klasen, Juergen
A1  - Krupkova, Olga
A1  - Würtz-Kozak, Karin
T1  - Expression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc
BT  - Association with Inflammation and Matrix Remodeling
JF  - International journal of molecular sciences
N2  - 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-1) or tumor necrosis factor alpha (TNF-) alone or in combination with TRPA1/V1 agonist allyl isothiocyanate (AITC, 3 and 10 mu M), 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 mu M 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.
KW  - low back pain
KW  - TRP channels
KW  - pro-inflammatory cytokines
KW  - aggrecanases
KW  - collagen
KW  - TRPA1
KW  - TRPV1
KW  - TRPV2
KW  - TRPV4
KW  - TRPC6
Y1  - 2019
U6  - https://doi.org/10.3390/ijms20071767
SN  - 1422-0067
VL  - 20
IS  - 7
PB  - MDPI
CY  - Basel
ER  -