Osteoarthritis (OA) has long been viewed as a degenerative “wear-and-tear” disease of cartilage. There is, however, increasing evidence to confirm that inflammation has a critical role in the pathogenesis and symptoms of the disease. Inflammation in osteoarthritis is distinct from that typical for rheumatoid arthritis; it is generally low-grade in its nature but characterized by exacerbations with joint effusions and more severe symptoms. Osteoarthritis shares many features of innate immunity but the inflammatory mechanisms eventually leading to anatomical and functional changes and symptoms typical for osteoarthritis are not known in detail; but their further understanding is essential for the development of disease-modifying treatments for osteoarthritis.
Transient receptor potential ankyrin 1 (TRPA1) is a ligand-gated membrane-bound cation channel. It has been widely studied in sensory neurons where it acts as a chemosensor for harmful exogenous compounds and mediates pain and neurogenic inflammation. More recently, TRPA1 has been found to be activated also by endogenous compounds formed in inflammation, such as reactive oxygen and nitrogen species. That prompted us to investigate the role of TRPA1 in inflammatory conditions including osteoarthritis.
Monosodium iodoacetate (MIA) -induced arthritis is a widely used animal model of osteoarthritis. We found that MIA evoked acute inflammation, degenerative cartilage changes and joint pain in wild type mice; but interestingly, those responses were significantly attenuated in TRPA1 deficient animals. Furthermore, TRPA1 was found to be expressed and inducible by inflammatory factors including IL-1 and IL-17 in primary human OA chondrocytes; and the TRPA1 channel was shown to be functional based on calcium influx assays. Pharmacological inhibition and genetic depletion of TRPA1 downregulated the production of inflammatory factors and MMP enzymes in mouse cartilage and primary human OA chondrocytes.
The present results introduce TRPA1 as a plausible factor involved in the pathogenesis of OA and provide a novel target for analgesic and anti-inflammatory drugs with disease modifying potential in OA.
Disclosure of Interest None declared
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