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Recently, we have discovered that TRPA1 is also expressed in human osteoarthritic (OA) chondrocytes and downregulated by the anti-inflammatory drugs aurothiomalate and dexamethasone. We have also shown TRPA1 to mediate inflammation, pain, and cartilage degeneration in experimental osteoarthritis. In this study, we investigated the role of TRPA1 in joint inflammation, focusing on the pro-inflammatory cytokine interleukin-6 (IL-6). We utilized cartilage\/chondrocytes from wild-type (WT) and TRPA1 knockout (KO) mice, along with primary chondrocytes from OA patients. The results show that TRPA1 regulates the synthesis of the OA-driving inflammatory cytokine IL-6 in chondrocytes. IL-6 was highly expressed in WT chondrocytes, and its expression, along with the expression of IL-6 family cytokines leukemia inhibitory factor (LIF) and IL-11, were significantly downregulated by TRPA1 deficiency. Furthermore, treatment with the TRPA1 antagonist significantly downregulated the expression of IL-6 in chondrocytes from WT mice and OA patients. The results suggest that TRPA1 is involved in the upregulation of IL-6 production in chondrocytes. These findings together with previous results on the expression and functions of TRPA1 in cellular and animal models point to the role of TRPA1 as a potential mediator and novel drug target in osteoarthritis.<\/jats:p>","DOI":"10.3390\/ijms22010087","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T12:19:51Z","timestamp":1608725991000},"page":"87","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Transient Receptor Potential Ankyrin 1 (TRPA1) Is Involved in Upregulating Interleukin-6 Expression in Osteoarthritic Chondrocyte Models"],"prefix":"10.3390","volume":"22","author":[{"given":"Elina","family":"Nummenmaa","sequence":"first","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"H\u00e4m\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8187-1216","authenticated-orcid":false,"given":"Antti","family":"Pemmari","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri J.","family":"Moilanen","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri","family":"Tuure","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riina M.","family":"Nieminen","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teemu","family":"Moilanen","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, FI-33014 Tampere, Finland"},{"name":"Coxa Hospital for Joint Replacement, FI-33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katriina","family":"Vuolteenaho","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8577-0316","authenticated-orcid":false,"given":"Eeva","family":"Moilanen","sequence":"additional","affiliation":[{"name":"The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, FI-33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/978-3-642-54215-2_23","article-title":"Trpa1","volume":"222","author":"Zygmunt","year":"2014","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/bcpt.12138","article-title":"TRPA1: A transducer and amplifier of pain and inflammation","volume":"114","author":"Koivisto","year":"2014","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"12248","DOI":"10.1073\/pnas.0505356102","article-title":"Pungent products from garlic activate the sensory ion channel TRPA1","volume":"102","author":"Bautista","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/nature02282","article-title":"Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1","volume":"427","author":"Jordt","year":"2004","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0896-6273(04)00150-3","article-title":"Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin","volume":"41","author":"Bandell","year":"2004","journal-title":"Neuron"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.neulet.2008.04.007","article-title":"TRPA1 receptor localisation in the human peripheral nervous system and functional studies in cultured human and rat sensory neurons","volume":"438","author":"Anand","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"31962","DOI":"10.1074\/jbc.M112.361139","article-title":"Hypoxia-inducible factor-1alpha (HIF1alpha) switches on transient receptor potential ankyrin repeat 1 (TRPA1) gene expression via a hypoxia response element-like motif to modulate cytokine release","volume":"287","author":"Hatano","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s13075-016-1080-4","article-title":"Transient receptor potential ankyrin 1 (TRPA1) is functionally expressed in primary human osteoarthritic chondrocytes","volume":"18","author":"Nummenmaa","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nassini, R., Pedretti, P., Moretto, N., Fusi, C., Carnini, C., Facchinetti, F., Viscomi, A.R., Pisano, A.R., Stokesberry, S., and Brunmark, C. (2012). Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042454"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/nchembio821","article-title":"Nitric oxide activates TRP channels by cysteine S-nitrosylation","volume":"2","author":"Yoshida","year":"2006","journal-title":"Nat. Chem. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1523\/JNEUROSCI.5369-07.2008","article-title":"Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress","volume":"28","author":"Andersson","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1007\/s13238-017-0395-5","article-title":"TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: Pro-inflammatory response induced by their activation and their sensitization","volume":"8","author":"Gouin","year":"2017","journal-title":"Protein Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.rehab.2016.07.004","article-title":"An update on the pathophysiology of osteoarthritis","volume":"59","author":"Mobasheri","year":"2016","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.bone.2016.01.019","article-title":"Inflammatory mediators in osteoarthritis: A critical review of the state-of-the-art, current prospects, and future challenges","volume":"85","author":"Rahmati","year":"2016","journal-title":"Bone"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"561459","DOI":"10.1155\/2014\/561459","article-title":"The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis","volume":"2014","author":"Wojdasiewicz","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrrheum.2010.196","article-title":"Role of proinflammatory cytokines in the pathophysiology of osteoarthritis","volume":"7","author":"Kapoor","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8293921","DOI":"10.1155\/2020\/8293921","article-title":"The Role of Inflammation in the Pathogenesis of Osteoarthritis","volume":"2020","author":"Chow","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1016\/j.joca.2015.09.008","article-title":"Monosodium Iodoacetate-Induced Inflammation and Joint Pain are Reduced in TRPA1 Deficient mice\u2014Potential Role of TRPA1 in Osteoarthritis","volume":"23","author":"Moilanen","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e000556","DOI":"10.1136\/rmdopen-2017-000556","article-title":"TRPA1 expression is downregulated by dexamethasone and aurothiomalate in human chondrocytes: TRPA1 as a novel factor and drug target in arthritis","volume":"3","author":"Nummenmaa","year":"2017","journal-title":"RMD Open"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Moilanen, L.J., H\u00e4m\u00e4l\u00e4inen, M., Lehtim\u00e4ki, L., Nieminen, R.M., and Moilanen, E. (2015). Urate crystal induced inflammation and joint pain are reduced in transient receptor potential ankyrin 1 deficient mice\u2014Potential role for transient receptor potential ankyrin 1 in gout. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117770"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13075-015-0904-y","article-title":"Transient receptor potential ankyrin 1 (TRPA1) receptor is involved in chronic arthritis: In vivo study using TRPA1-deficient mice","volume":"18","author":"Horvath","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13075-015-0905-x","article-title":"Environmental cold exposure increases blood flow and affects pain sensitivity in the knee joints of CFA-induced arthritic mice in a TRPA1-dependent manner","volume":"18","author":"Fernandes","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2984","DOI":"10.1002\/art.38112","article-title":"Transient receptor potential ankyrin 1 receptor stimulation by hydrogen peroxide is critical to trigger pain during monosodium urate-induced inflammation in rodents","volume":"65","author":"Trevisan","year":"2013","journal-title":"Arthritis. Rheum."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1021\/acschemneuro.9b00083","article-title":"Pyrazine-Fused Triterpenoids Block the TRPA1 Ion Channel in Vitro and Inhibit TRPA1-Mediated Acute Inflammation in Vivo","volume":"10","author":"Moilanen","year":"2019","journal-title":"ACS. Chem. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/srep00380","article-title":"TRPA1 contributes to the acute inflammatory response and mediates carrageenan-induced paw edema in the mouse","volume":"2","author":"Moilanen","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1124\/mol.108.054445","article-title":"Nitrooleic acid, an endogenous product of nitrative stress, activates nociceptive sensory nerves via the direct activation of TRPA1","volume":"75","author":"Ghatta","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nummenmaa, E. (2020). TRPA1 as a Novel Factor and Drug Target in Osteoarthritis. [Ph.D. Thesis, Tampere University].","DOI":"10.1016\/j.joca.2019.02.372"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Laavola, M., Lepp\u00e4nen, T., H\u00e4m\u00e4l\u00e4inen, M., Vuolteenaho, K., Moilanen, T., Nieminen, R., and Moilanen, E. (2018). IL-6 in Osteoarthritis: Effects of Pine Stilbenoids. Molecules, 24.","DOI":"10.3390\/molecules24010109"},{"key":"ref_30","first-page":"215140","article-title":"YKL-40 as a novel factor associated with inflammation and catabolic mechanisms in osteoarthritic joints","volume":"2014","author":"Koskinen","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"499","DOI":"10.4049\/jimmunol.144.2.499","article-title":"IL-6 production by human articular chondrocytes. Modulation of its synthesis by cytokines, growth factors, and hormones in vitro","volume":"144","author":"Guerne","year":"1990","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/13684730050515796","article-title":"Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis","volume":"6","author":"Kaneko","year":"2000","journal-title":"Cytokines Cell. Mol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1016\/j.joca.2015.05.035","article-title":"Interleukin-6 and tumor necrosis factor alpha in synovial fluid are associated with progression of radiographic knee osteoarthritis in subjects with previous meniscectomy","volume":"23","author":"Larsson","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1002\/art.24598","article-title":"Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: The Chingford Study","volume":"60","author":"Livshits","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/j.joca.2010.08.016","article-title":"Circulating levels of IL-6 and TNF-alpha are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults","volume":"18","author":"Stannus","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.joca.2013.08.014","article-title":"Synovial fluid levels of bradykinin correlate with biochemical markers for cartilage degradation and inflammation in knee osteoarthritis","volume":"21","author":"Bellucci","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1002\/art.10943","article-title":"The role of the interleukin-6 family of cytokines in inflammatory arthritis and bone turnover","volume":"48","author":"Wong","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1172\/JCI115964","article-title":"Leukemia inhibitory factor is expressed in cartilage and synovium and can contribute to the pathogenesis of arthritis","volume":"90","author":"Lotz","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3928\/01477447-20140430-57","article-title":"Tissue levels of leukemia inhibitory factor vary by osteoarthritis grade","volume":"37","author":"Jiang","year":"2014","journal-title":"Orthopedics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1016\/j.joca.2016.03.007","article-title":"Gene expression changes in damaged osteoarthritic cartilage identify a signature of non-chondrogenic and mechanical responses","volume":"24","author":"Dunn","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0009-9120(98)00062-9","article-title":"Comparative study of serum and synovial fluid interleukin-11 levels in patients with various arthritides","volume":"31","author":"Trontzas","year":"1998","journal-title":"Clin. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cytogfr.2003.10.005","article-title":"IL-6, RANKL, TNF-alpha\/IL-1: Interrelations in bone resorption pathophysiology","volume":"15","author":"Padrines","year":"2004","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_43","unstructured":"ClinicalTrials.gov (2020, September 15). A Clinical Trial to Study the Effect of the Interleukin-6 Receptor Antagonist Tocilizumab in Patients with Hand Osteoarthritis, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02477059."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3747\/pdi.2016.00290","article-title":"TRPA1 Mechanoreceptors Mediate the IL-6 Response to a Single PD Dwell in the Rat","volume":"37","author":"Nilsson","year":"2017","journal-title":"Perit. Dial. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1096\/fj.13-229948","article-title":"TRPA1 controls inflammation and pruritogen responses in allergic contact dermatitis","volume":"27","author":"Liu","year":"2013","journal-title":"FASEB. J."},{"key":"ref_46","unstructured":"ClinicalTrials.gov (2020, September 15). A Clinical Trial to Study the Effects of GRC 17536 in Patients with Painful Diabetic Peripheral Neuropathy, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01726413."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/35036035","article-title":"The versatility and universality of calcium signalling","volume":"1","author":"Berridge","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/jor.21239","article-title":"The catabolic role of toll-like receptor 2 (TLR-2) mediated by the NF-kappaB pathway in septic arthritis","volume":"29","author":"Papathanasiou","year":"2011","journal-title":"J. Orthop. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1002\/art.27755","article-title":"The CCL5\/CCR5 axis promotes interleukin-6 production in human synovial fibroblasts","volume":"62","author":"Tang","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.immuni.2013.11.021","article-title":"Proatherogenic conditions promote autoimmune T helper 17 cell responses in vivo","volume":"40","author":"Lim","year":"2014","journal-title":"Immunity"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1476-9255-4-5","article-title":"The role of the purinergic P2X7 receptor in inflammation","volume":"4","author":"Lister","year":"2007","journal-title":"J. Inflamm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.immuni.2010.05.001","article-title":"Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans","volume":"32","author":"Saijo","year":"2010","journal-title":"Immunity"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.cyto.2007.09.013","article-title":"Interleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cells","volume":"40","author":"Moulin","year":"2007","journal-title":"Cytokine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1136\/ard.59.6.448","article-title":"Expression of thrombospondin-1 and its receptor CD36 in human osteoarthritic cartilage","volume":"59","author":"Pfander","year":"2000","journal-title":"Ann. Rheum. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1002\/art.24305","article-title":"Inhibition of interleukin-33 signaling attenuates the severity of experimental arthritis","volume":"60","author":"Palmer","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Dosch, M., Gerber, J., Jebbawi, F., and Beldi, G. (2018). Mechanisms of ATP Release by Inflammatory Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041222"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1177\/0022034514544507","article-title":"TRPA1 and TRPV4 activation in human odontoblasts stimulates ATP release","volume":"93","author":"Egbuniwe","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/1744-8069-10-75","article-title":"Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl","volume":"10","author":"Ide","year":"2014","journal-title":"Mol. Pain."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1242\/jcs.112.3.297","article-title":"Human primary fibroblasts in vitro express a purinergic P2X7 receptor coupled to ion fluxes, microvesicle formation and IL-6 release","volume":"112","author":"Solini","year":"1999","journal-title":"J. Cell Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.neuron.2006.03.042","article-title":"TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction","volume":"50","author":"Kwan","year":"2006","journal-title":"Neuron"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.intimp.2019.03.014","article-title":"Downregulation of microsomal prostaglandin E synthase-1 (mPGES-1) expression in chondrocytes is regulated by MAP kinase phosphatase-1 (MKP-1)","volume":"71","author":"Tuure","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/978-1-4939-1619-1_2","article-title":"Primary murine growth plate and articular chondrocyte isolation and cell culture","volume":"1226","author":"Jonason","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1136\/ard.2009.113100","article-title":"EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis","volume":"69","author":"Zhang","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1111\/bph.15142","article-title":"Regulation of gene expression by MF63, doi:a selective inhibitor of microsomal PGE synthase 1 (mPGES1) in human osteoarthritic chondrocytes","volume":"177","author":"Tuure","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_65","unstructured":"Andrews, A. (2020, November 22). FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc."},{"key":"ref_66","unstructured":"Bolger, A., and Giorgi, F. (2020, November 22). Trimmomatic: A Flexible Read Trimming Tool for Illumina NGS Data. Available online: http:\/\/www.usadellab.org\/cms\/index.php."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nmeth.1226","article-title":"Mapping and quantifying mammalian transcriptomes by RNA-Seq","volume":"5","author":"Mortazavi","year":"2008","journal-title":"Nat. Methods"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3109\/03009742.2014.1000372","article-title":"Effects of FGF-2 and FGF receptor antagonists on MMP enzymes, aggrecan, and type II collagen in primary human OA chondrocytes","volume":"44","author":"Nummenmaa","year":"2015","journal-title":"Scand. J. Rheumatol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/1\/87\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:49:02Z","timestamp":1760179742000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/1\/87"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,23]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["ijms22010087"],"URL":"https:\/\/doi.org\/10.3390\/ijms22010087","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,23]]}}}