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To date, research into mitochondrial dynamics in IVDD is at an early stage. Since Piezo1 is a novel Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010permeable channel, we asked whether Piezo1 could modulate mitochondrial fission through Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signalling during CEP degeneration. In\u00a0vitro and in\u00a0vivo models of inflammation\u2010induced CEP degeneration were established with lipopolysaccharide (LPS). We found increased expression of Piezo1 in degenerated CEP tissues and LPS\u2010treated CEP cells. The Piezo1 activator Yoda1 exacerbated CEP cell senescence and apoptosis by triggering Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx. Yoda1 also induced mitochondrial fragmentation and dysfunction. In contrast, the Piezo1 inhibitor GsMTx4 exerted cytoprotective effects in LPS\u2010treated CEP cells. Additionally, the CaMKII inhibitor KN\u201093 reversed Yoda1\u2010induced mitochondrial fission and restored mitochondrial function. Mechanistically, the phosphorylation and mitochondrial translocation of Drp1 were regulated by the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \/CaMKII signalling. The Drp1 inhibitor Mdivi\u20101 suppressed mitochondrial fission, then reduced mitochondrial dysfunction and CEP cell death. Moreover, knockdown of Piezo1 by siRNA hindered CaMKII and Drp1 activation, facilitating the redistribution of mitochondrial Drp1 to the cytosol in LPS\u2010treated CEP cells. Piezo1 silencing improved mitochondrial morphology and function, thereby rescuing CEP cell senescence and apoptosis under inflammatory conditions. Finally, subendplate injection of GsMTx4 or AAV\u2010shPiezo1 alleviated CEP degeneration in a rat model. Thus, Piezo1 may exacerbate inflammation\u2010induced CEP degeneration by triggering mitochondrial fission and dysfunction via the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \/CaMKII\/Drp1 axis.\n                  <\/jats:p>","DOI":"10.1111\/acel.14440","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T01:34:25Z","timestamp":1732844065000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Piezo1 exacerbates inflammation\u2010induced cartilaginous endplate degeneration by activating mitochondrial fission via the Ca\n                    <sup>2+<\/sup>\n                    \/\n                    <scp>CaMKII<\/scp>\n                    \/Drp1 axis"],"prefix":"10.1111","volume":"24","author":[{"given":"Zhidi","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feizhou","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai 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