TY - JOUR T1 - TRPA1 expression is downregulated by dexamethasone and aurothiomalate in human chondrocytes: TRPA1 as a novel factor and drug target in arthritis JF - RMD Open JO - RMD Open DO - 10.1136/rmdopen-2017-000556 VL - 3 IS - 2 SP - e000556 AU - Elina Nummenmaa AU - Mari Hämäläinen AU - Lauri J Moilanen AU - Teemu Moilanen AU - Katriina Vuolteenaho AU - Eeva Moilanen Y1 - 2017/09/01 UR - http://rmdopen.bmj.com/content/3/2/e000556.abstract N2 - Key messagesWhat is already known about this subject?Transient receptor potential ankyrin 1 (TRPA1) is a membrane-associated cation channel primarily studied in sensory neurons, where it acts as a chemosensor of pungent compounds and mediates pain.TRPA1 has recently emerged as a potential factor/mediator in arthritis; we have shown TRPA1 to mediate inflammatory and catabolic responses in primary human chondrocytes, as well as cartilage degradation, inflammation and pain in an experimental model of arthritis.What does this study add?This study shows that anti-inflammatory drugs dexamethasone and aurothiomalate downregulate the expression of functional TRPA1 in human chondrocytes.How might this impact on clinical practice?These results show a previously unknown mechanism of action for dexamethasone and aurothiomalate via downregulation of TRPA1, and thus provides a novel concept for the development of drugs for arthritis with analgesic and disease modifying properties.Transient receptor potential ankyrin 1 (TRPA1) is a ligand-gated membrane-bound cation channel. TRPA1 has been largely studied in neurons, where it mediates pain and neurogenic inflammation and acts as a chemosensor for harmful exogenous compounds.1 2 More recently, TRPA1 has been found to be activated also by endogenous compounds formed in inflammatory conditions characteristic to arthritis, such as reactive oxygen and nitrogen species.3We have recently discovered that TRPA1 is functionally expressed in primary human osteoarthritic chondrocytes,4 where it upregulated the production of mediators related to arthritis: interleukin (IL)-6, prostaglandin E2 and matrix metalloproteinases 1, 3 and 13.4 Furthermore, we showed in monosodium iodoacetate-induced experimental arthritis that TRPA1 activation mediates inflammation, cartilage degradation and … ER -