Transient receptor potential ankyrin 1 TRPA1 is functionally expressed in primary human osteoarthritic chondrocytesReport as inadecuate




Transient receptor potential ankyrin 1 TRPA1 is functionally expressed in primary human osteoarthritic chondrocytes - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 18:185

First Online: 11 August 2016Received: 03 March 2016Accepted: 21 July 2016

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 Ca-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 Ca 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.

KeywordsOsteoarthritis Chondrocyte TRPA1 Inflammation Matrix metalloproteinase Electronic supplementary materialThe online version of this article doi:10.1186-s13075-016-1080-4 contains supplementary material, which is available to authorized users.

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Author: Elina Nummenmaa - Mari Hämäläinen - Lauri J. Moilanen - Erja-Leena Paukkeri - Riina M. Nieminen - Teemu Moilanen - Katr

Source: https://link.springer.com/







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