{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:30:54Z","timestamp":1785148254066,"version":"3.55.0"},"reference-count":132,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The catabolic and destructive activity of serine proteases in arthritic joints is well known; however, these enzymes can also signal pain and inflammation in joints. For example, thrombin, trypsin, tryptase, and neutrophil elastase cleave the extracellular N-terminus of a family of G protein-coupled receptors and the remaining tethered ligand sequence then binds to the same receptor to initiate a series of molecular signalling processes. These protease activated receptors (PARs) pervade multiple tissues and cells throughout joints where they have the potential to regulate joint homeostasis. Overall, joint PARs contribute to pain, inflammation, and structural integrity by altering vascular reactivity, nociceptor sensitivity, and tissue remodelling. This review highlights the therapeutic potential of targeting PARs to alleviate the pain and destructive nature of elevated proteases in various arthritic conditions.<\/jats:p>","DOI":"10.3390\/ijms22179352","type":"journal-article","created":{"date-parts":[[2021,8,29]],"date-time":"2021-08-29T21:45:16Z","timestamp":1630273516000},"page":"9352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Protease Activated Receptors and Arthritis"],"prefix":"10.3390","volume":"22","author":[{"given":"Flora","family":"Lucena","sequence":"first","affiliation":[{"name":"Departments of Pharmacology and Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4529-3428","authenticated-orcid":false,"given":"Jason J.","family":"McDougall","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,28]]},"reference":[{"key":"ref_1","first-page":"646","article-title":"Burden of major muskuloskeletal conditions","volume":"81","author":"Woolf","year":"2003","journal-title":"Bull. 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