Abstract
BackgroundTransient receptor potential ankyrin 1 (TRPA1) is a membrane-associated cation channel, widely expressed in neuronal cells and involved in nociception and neurogenic inflammation. We showed recently that TRPA1 mediates cartilage degradation and joint pain in the MIA-model of osteoarthritis (OA) suggesting a hitherto unknown role for TRPA1 in OA. Therefore, we aimed to investigate whether TRPA1 is expressed and functional in human OA chondrocytes.MethodsExpression of TRPA1 in primary human OA chondrocytes was assessed by qRT-PCR and Western blot. The functionality of the TRPA1 channel was assessed by Ca2+-influx measurements. Production of MMP-1, MMP-3, MMP-13, IL-6, and PGE2 subsequent to TRPA1 activation was measured by immunoassay.ResultsWe show here for the first time that TRPA1 is expressed in primary human OA chondrocytes and its expression is increased following stimulation with inflammatory factors IL-1β, IL-17, LPS, and resistin. Further, the TRPA1 channel was found to be functional, as stimulation with the TRPA1 agonist AITC caused an increase in Ca2+ influx, which was attenuated by the TRPA1 antagonist HC-030031. Genetic depletion and pharmacological inhibition of TRPA1 downregulated the production of MMP-1, MMP-3, MMP-13, IL-6, and PGE2 in osteoarthritic chondrocytes and murine cartilage, respectively.ConclusionsThe TRPA1 cation channel was found to be functionally expressed in primary human OA chondrocytes, which is an original finding. The presence and inflammatory and catabolic effects of TRPA1 in human OA chondrocytes propose a highly intriguing role for TRPA1 as a pathogenic factor and drug target in OA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1080-4) contains supplementary material, which is available to authorized users.
Highlights
Transient receptor potential ankyrin 1 (TRPA1) is a membrane-associated cation channel, widely expressed in neuronal cells and involved in nociception and neurogenic inflammation
Very recently we found that TRPA1 has a role in mediating acute inflammation, cartilage destruction, and joint pain in monosodium iodoacetate (MIA)induced inflammation and osteoarthritis in the mouse [27]
The proinflammatory cytokine IL-1β was found to increase TRPA1 expression in a time-dependent manner: in primary chondrocytes the expression of TRPA1 increased up to 48 hours and declined thereafter (Fig. 1a), whereas in the human T/C28a2 chondrocytes the expression maximum was at 6 hours (Fig. 1b)
Summary
Transient receptor potential ankyrin 1 (TRPA1) is a membrane-associated cation channel, widely expressed in neuronal cells and involved in nociception and neurogenic inflammation. Transient receptor potential ankyrin 1 (TRPA1) is a membrane-associated cation channel which mediates pain and hyperalgesia [1, 2] and functions as a chemosensor of noxious compounds [3,4,5]. TRPA1 was first discovered in 1999 [6] and has since been found to be widely expressed in afferent sensory neurons, especially in Aδ and C fibers of nociceptors [7, 8]. TRPA1 has a role in mediating neurogenic inflammation [9, 10]. The activation of TRPA1 causes an influx of cation ions, Ca2+, into the activated cells [16] and this elevation of intracellular Ca2+ has been
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