{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:24:26Z","timestamp":1791566666937,"version":"4.3.4"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"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>Osteoarthritis (OA) is the most common degenerative joint disease causing pain and functional limitations. Physical activity as a clinically relevant, effective intervention alleviates pain and promotes joint function. In chondrocytes, perception and transmission of mechanical signals are controlled by mechanosensitive ion channels, whose dysfunction in OA chondrocytes is leading to disease progression. Signaling of mechanosensitive ion channels Piezo\/TRPV4 was analyzed by Yoda1\/GSK1016790A application and calcium-imaging of Fura-2-loaded chondrocytes. Expression analysis was determined by qPCR and immunofluorescence in healthy vs. OA chondrocytes. Chondrocytes were mechanically stimulated using the Flexcell\u2122 technique. Yoda1 and GSK1016790A caused an increase in intracellular calcium [Ca2+]i for Yoda1, depending on extracellularly available Ca2+. When used concomitantly, the agonist applied first inhibited the effect of subsequent agonist application, indicating mutual interference between Piezo\/TRPV4. Yoda1 increased the expression of metalloproteinases, bone-morphogenic protein, and interleukins in healthy and OA chondrocytes to a different extent. Flexcell\u2122-induced changes in the expression of MMPs and ILs differed from changes induced by Yoda1. We conclude that Piezo1\/TRPV4 communicate with each other, an interference that may be impaired in OA chondrocytes. It is important to consider that mechanical stimulation may have different effects on OA depending on its intensity.<\/jats:p>","DOI":"10.3390\/ijms24097868","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T02:30:52Z","timestamp":1682476252000},"page":"7868","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Activation of the Mechanosensitive Ion Channels Piezo1 and TRPV4 in Primary Human Healthy and Osteoarthritic Chondrocytes Exhibits Ion Channel Crosstalk and Modulates Gene Expression"],"prefix":"10.3390","volume":"24","author":[{"given":"Bibiane","family":"Steinecker-Frohnwieser","sequence":"first","affiliation":[{"name":"Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Thorerstra\u00dfe 26, 5760 Saalfelden, Austria"},{"name":"Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Spitalgasse 23, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3156-7902","authenticated-orcid":false,"given":"Birgit","family":"Lohberger","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Spitalgasse 23, 1090 Vienna, Austria"},{"name":"Department of Orthopedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Toegel","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Spitalgasse 23, 1090 Vienna, Austria"},{"name":"Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-1804","authenticated-orcid":false,"given":"Reinhard","family":"Windhager","sequence":"additional","affiliation":[{"name":"Karl Chiari Lab for Orthopaedic Biology, Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Glanz","sequence":"additional","affiliation":[{"name":"Department of Special Anaesthesia and Pain Therapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Kratschmann","sequence":"additional","affiliation":[{"name":"Department of Special Anaesthesia and Pain Therapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2598-2325","authenticated-orcid":false,"given":"Andreas","family":"Leithner","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma, Medical University of Graz, Auenbruggerplatz 5, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Weigl","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Spitalgasse 23, 1090 Vienna, Austria"},{"name":"Department of Special Anaesthesia and Pain Therapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1002\/art.42089","article-title":"Prevalence Trends of Site-Specific Osteoarthritis from 1990 to 2019: Findings from the Global Burden of Disease Study 2019","volume":"74","author":"Long","year":"2022","journal-title":"Arthritis. 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