Transient receptor potential ankyrin 1 (TRPA1) is functionally expressed in primary human osteoarthritic chondrocytes

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.

TRPA1 expression is downregulated by dexamethasone and aurothiomalate in human chondrocytes: TRPA1 as a novel factor and drug target in arthritis

“…Human T/C28a2 chondrocytes 6 were cultured with the aforementioned drugs, along with IL-1β, which was recently found to upregulate TRPA1 expression in chondrocytes. 4 Dexamethasone and aurothiomalate inhibited TRPA1 mRNA expression in a dose-dependent manner ( figure 1A ), while methotrexate (10 µM), sulfasalazine (10 µM), hydroxychloroquine (10 µM) and ibuprofen (10 µM) had no effect. Dexamethasone and aurothiomalate also decreased TRPA1 protein levels ( figure 1C ).…”

“…We 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 E 2 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 pain. 5 TRPA1 thus emerges as a novel factor associated with arthritis.…”

Transient Receptor Potential Ankyrin 1 Enhances Ovalbumin-Induced Acute Allergic Inflammation in Murine Models

“…For example, inflammatory edema caused by TRPA1 activation is dependent on classical inflammatory mechanisms such as mast cell degranulation, neutrophil migration, the release of histamine, serotonin, and adrenalin, and the production of prostaglandins [6, 36]. Activation of TRPA1 has also been shown to enhance the expression of some inflammatory genes such as the prostaglandin-producing enzyme COX-2, myeloperoxidase, IL-6, and IL-1β [6, 9, 10, 21, 37, 38]. …”

Hip Joint Osteoarthritis Pain Sources and Control

“…As noted above, the topic of osteoarthritic hip joint pain is a complex one, where pain may originate both within and outside the joint [29] with no degree of consistency, given the whole joint, including muscles, bone, ligaments, and joint capsule may be subject to degenerative and inflammatory changes. As well, despite the fact that articular cartilage, the key involved tissue in osteoarthritis, is commonly cited as having no nerve supply [31], this tissue when damaged may yet produce pain via the transient receptor potential ankyrin 1 (TRPA1), a membrane-associated cation channel, widely expressed in neuronal cells and involved in nociception and neurogenic inflammation processes [32]. Pain expression in hip osteoarthritis is also expected to be non-uniform even if the same tissue is involved, and can occur in acute versus chronic forms, and as a result of central as well as peripheral influences or both [33].…”