{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:05:57Z","timestamp":1790802357321,"version":"4.1.0"},"reference-count":101,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008569","name":"Oklahoma Center for the Advancement of Science and Technology","doi-asserted-by":"crossref","award":["HR21-119"],"award-info":[{"award-number":["HR21-119"]}],"id":[{"id":"10.13039\/100008569","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, synovial inflammation, osteophyte formation, joint space narrowing, and persistent pain. During OA progression, synovial inflammation triggers the release of pro-inflammatory cytokines, including IL-1\u03b2, TNF-\u03b1, and IL-6, which activate matrix metalloproteinases (MMPs) and aggrecanases, driving extracellular matrix (ECM) degradation. Emerging evidence indicates that transient receptor potential (TRP) channels, via calcium (Ca2+) signaling, function as molecular sensors in joint tissues, including chondrocytes, synoviocytes, sensory neurons, and regulate cartilage homeostasis, synovial inflammation, and OA pain. In cartilage, TRP channels govern chondrocyte survival, mechanotransduction, autophagy, oxidative stress, and ECM turnover, thereby modulating cartilage homeostasis. In synovial tissue, TRP channels regulate inflammatory signaling and cytokine, chemokine, and matrix-degrading enzyme production, leading to synovitis and joint destruction. In sensory neurons innervating the joint, TRP channels respond to mechanical and inflammatory stimuli, increasing nociceptor excitability, neuropeptide release, and pain sensitization, driving OA pain. TRP channel signaling also modulates immune cell infiltration and macrophage-driven inflammation, sustaining chronic pain and tissue damage in OA. This review summarizes emerging evidence on TRP channel functions in OA pathogenesis and highlights their potential as therapeutic targets to alleviate inflammation, protect cartilage, and reduce OA-associated pain.<\/jats:p>","DOI":"10.3390\/cells15030299","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:35:37Z","timestamp":1770287737000},"page":"299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Emerging Role of TRP Channels in Osteoarthritis Pathogenesis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8058-9731","authenticated-orcid":false,"given":"Shivmurat","family":"Yadav","sequence":"first","affiliation":[{"name":"Department of Medicine, College of Medicine, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoti","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA"},{"name":"Department of Cell Biology, College of Medicine, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0042-4068","authenticated-orcid":false,"given":"Mary Beth","family":"Humphrey","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA"},{"name":"Department of Cell Biology, College of Medicine, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA"},{"name":"Department of Veterans Affairs, Oklahoma City, OK 73111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"C424","DOI":"10.1152\/ajpcell.00553.2005","article-title":"Thermosensitive TRP ion channels mediate cytosolic calcium response in human synoviocytes","volume":"291","author":"Kochukov","year":"2006","journal-title":"Am. 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