title: Transient receptor potential ankyrin 1 (TRPA1) is functionally expressed in primary human osteoarthritic chondrocytes.
abstract: Transient 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.
  
  
  
  Expression 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(2+)-influx measurements. Production of MMP-1, MMP-3, MMP-13, IL-6, and PGE2 subsequent to TRPA1 activation was measured by immunoassay.
  
  
  
  We 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(2+) 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.
  
  
  
  The 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.
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors: Elina
authors: 0000-0001-7041-2375
authors: E
authors: Nummenmaa
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors: Mari
authors: M
authors: Hämäläinen
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors: Lauri J
authors: LJ
authors: Moilanen
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors: Erja-Leena
authors: EL
authors: Paukkeri
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors: Riina M
authors: RM
authors: Nieminen
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.|Coxa Hospital for Joint Replacement, Tampere, Finland.
authors: Teemu
authors: T
authors: Moilanen
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.
authors: Katriina
authors: K
authors: Vuolteenaho
authors: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. eeva.moilanen@uta.fi.
authors: Eeva
authors: E
authors: Moilanen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015220:Calcium Channels / Q000032:analysis / Q000096:biosynthesis*; D002358:Cartilage, Articular / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis*; D010003:Osteoarthritis / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels
keywords: Chondrocyte; Inflammation; Matrix metalloproteinase; Osteoarthritis; TRPA1