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

TitleExpression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc: Association with Inflammation and Matrix Remodeling
Authors
KeywordsAggrecanases
Collagen
Low back pain
Pro-inflammatory cytokines
TRP channels
TRPA1
TRPC6
TRPV1
TRPV2
TRPV4
Issue Date2019
PublisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms
Citation
International Journal of Molecular Sciences, 2019, v. 20 n. 7, article no. 1767 How to Cite?
AbstractTransient 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.
Persistent Identifierhttp://hdl.handle.net/10722/272058
ISSN
2018 Impact Factor: 4.183
2015 SCImago Journal Rankings: 1.160
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorKameda, T-
dc.contributor.authorZvick, J-
dc.contributor.authorVuk, M-
dc.contributor.authorSadowska, A-
dc.contributor.authorTam, WK-
dc.contributor.authorLeung, VY-
dc.contributor.authorBölcskei, K-
dc.contributor.authorHelyes, Z-
dc.contributor.authorApplegate, LA-
dc.contributor.authorHausmann, ON-
dc.contributor.authorKlasen, J-
dc.contributor.authorKrupkova, O-
dc.contributor.authorWuertz-Kozak, K-
dc.date.accessioned2019-07-20T10:34:50Z-
dc.date.available2019-07-20T10:34:50Z-
dc.date.issued2019-
dc.identifier.citationInternational Journal of Molecular Sciences, 2019, v. 20 n. 7, article no. 1767-
dc.identifier.issn1422-0067-
dc.identifier.urihttp://hdl.handle.net/10722/272058-
dc.description.abstractTransient 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.-
dc.languageeng-
dc.publisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms-
dc.relation.ispartofInternational Journal of Molecular Sciences-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAggrecanases-
dc.subjectCollagen-
dc.subjectLow back pain-
dc.subjectPro-inflammatory cytokines-
dc.subjectTRP channels-
dc.subjectTRPA1-
dc.subjectTRPC6-
dc.subjectTRPV1-
dc.subjectTRPV2-
dc.subjectTRPV4-
dc.titleExpression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc: Association with Inflammation and Matrix Remodeling-
dc.typeArticle-
dc.identifier.emailTam, WK: tamwk1@hku.hk-
dc.identifier.emailLeung, VY: vicleung@hku.hk-
dc.identifier.authorityLeung, VY=rp01764-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/ijms20071767-
dc.identifier.pmid30974795-
dc.identifier.pmcidPMC6480240-
dc.identifier.scopuseid_2-s2.0-85064816588-
dc.identifier.hkuros299455-
dc.identifier.volume20-
dc.identifier.issue7-
dc.identifier.spagearticle no. 1767-
dc.identifier.epagearticle no. 1767-
dc.identifier.isiWOS:000465258100072-
dc.publisher.placeSwitzerland-

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