{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:36:11Z","timestamp":1784734571173,"version":"3.55.0"},"reference-count":62,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T00:00:00Z","timestamp":1554854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["SNF PP00P2_163678\/1"],"award-info":[{"award-number":["SNF PP00P2_163678\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011713","name":"EUROSPINE","doi-asserted-by":"publisher","award":["Eurospine 2016_4"],"award-info":[{"award-number":["Eurospine 2016_4"]}],"id":[{"id":"10.13039\/501100011713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010024","name":"Hungarian Science Foundation","doi-asserted-by":"publisher","award":["GINOP-2.3.2.-15-2016-00048"],"award-info":[{"award-number":["GINOP-2.3.2.-15-2016-00048"]}],"id":[{"id":"10.13039\/501100010024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010024","name":"Hungarian Science Foundation","doi-asserted-by":"publisher","award":["EFOP 3.6.2."],"award-info":[{"award-number":["EFOP 3.6.2."]}],"id":[{"id":"10.13039\/501100010024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u03b2) or tumor necrosis factor alpha (TNF-\u03b1) alone or in combination with TRPA1\/V1 agonist allyl isothiocyanate (AITC, 3 and 10 \u00b5M), 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 \u00b5M 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.<\/jats:p>","DOI":"10.3390\/ijms20071767","type":"journal-article","created":{"date-parts":[[2019,4,10]],"date-time":"2019-04-10T11:25:08Z","timestamp":1554895508000},"page":"1767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Expression and Activity of TRPA1 and TRPV1 in the Intervertebral Disc: Association with Inflammation and Matrix Remodeling"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8770-4884","authenticated-orcid":false,"given":"Takuya","family":"Kameda","sequence":"first","affiliation":[{"name":"Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093 Zurich, Switzerland"},{"name":"Department of Orthopaedic Surgery, Fukushima Medical University, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Zvick","sequence":"additional","affiliation":[{"name":"Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Vuk","sequence":"additional","affiliation":[{"name":"Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Sadowska","sequence":"additional","affiliation":[{"name":"Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Kit","family":"Tam","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Traumatology, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Y.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Traumatology, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kata","family":"B\u00f6lcskei","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, University of P\u00e9cs, H-7624 P\u00e9cs, Szigeti \u00fat 12., Hungary"},{"name":"J\u00e1nos Szent\u00e1gothai Research Centre, University of P\u00e9cs, H-7624 P\u00e9cs, Ifj\u00fas\u00e1g \u00fatja 20., Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Helyes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, University of P\u00e9cs, H-7624 P\u00e9cs, Szigeti \u00fat 12., Hungary"},{"name":"J\u00e1nos Szent\u00e1gothai Research Centre, University of P\u00e9cs, H-7624 P\u00e9cs, Ifj\u00fas\u00e1g \u00fatja 20., Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7346-9921","authenticated-orcid":false,"given":"Lee Ann","family":"Applegate","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal Medicine, Unit of Regenerative Therapy (UTR), University Hospital Lausanne, EPCR\/02 Chemin des Croisettes 22, 1066 Epalinges, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver N.","family":"Hausmann","sequence":"additional","affiliation":[{"name":"Neuro- and Spine Center, St. Anna Hospital, Sankt-Anna-Strasse 32, 6006 Luzern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Klasen","sequence":"additional","affiliation":[{"name":"Clinic Prodorso, Walchestrasse 15, 8006 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2041-8557","authenticated-orcid":false,"given":"Olga","family":"Krupkova","sequence":"additional","affiliation":[{"name":"Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-4629","authenticated-orcid":false,"given":"Karin","family":"Wuertz-Kozak","sequence":"additional","affiliation":[{"name":"Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093 Zurich, Switzerland"},{"name":"Sch\u00f6n Clinic Munich Harlaching, Spine Center, Academic Teaching Hospital and Spine Research Institute of the Paracelsus Medical University Salzburg (AU), Harlachinger Str. 51, 81547 Munich, Germany"},{"name":"Department of Health Sciences, University of Potsdam, Am Neuen Palais 10, 14469 Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0030-5898(03)00101-9","article-title":"Low back pain: An economic assessment in the United States","volume":"35","author":"Pai","year":"2004","journal-title":"Orthop. 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