{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T21:52:27Z","timestamp":1778363547432,"version":"3.51.4"},"reference-count":44,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Research Project of Changsha Health Commission","award":["KJ-B2023086"],"award-info":[{"award-number":["KJ-B2023086"]}]},{"name":"Research Project of Changsha Health Commission","award":["KJ-B2023092"],"award-info":[{"award-number":["KJ-B2023092"]}]},{"name":"program of Hunan Provincial Health Commission","award":["202208032486"],"award-info":[{"award-number":["202208032486"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Science Progress"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Orthodontic tooth movement (OTM) relies on mechanotransduction and inflammatory responses within the periodontal ligament (PDL). This study aimed to elucidate the role of transient receptor potential vanilloid 4 (TRPV4) in mediating mechanical force-induced pyroptosis in human PDL (hPDL) cells and its functional impact on osteoclast activation during OTM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      hPDL cells were isolated from premolars extracted for orthodontic reasons and characterized for stem cell properties (CD73+\/CD90+\/CD105+; CD34\u2212\/CD45\u2212). An in vitro OTM model was established by applying compressive force (0\u20132.0\u2005g\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ). Pyroptosis was assessed via qRT-PCR, Western blot, and immunofluorescence for NLRP3, caspase-1, GSDMD, and IL-1\u03b2. Osteoclast differentiation was evaluated in hPDL-PBMC co-cultures using TRAP staining, ELISA (RANKL\/OPG), and gene expression analysis (CTSK\/TRAP). TRPV4 activation was modulated using agonist GSK1016790A.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compressive force (1.5\u2005g\/cm\n                      <jats:sup>2<\/jats:sup>\n                      , 24\u2005h) significantly upregulated pyroptosis markers (NLRP3, cleaved caspase-1, N-GSDMD, IL-1\u03b2) and inflammatory mediators (COX2, TNF-\u03b1, IL-6, and IL-8). TRPV4 activation was mechanosensitive and enhanced by GSK1016790A, which amplified pyroptosis and subsequent RANKL secretion. In co-cultures, hPDL pyroptosis promoted osteoclast differentiation, evidenced by increased TRAP\u2009+\u2009multinucleated cells and elevated CTSK\/TRAP expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Mechanical force activates TRPV4 to drive NLRP3\/caspase-1-dependent pyroptosis in hPDL cells, which accelerates osteoclastogenesis via RANKL signaling. Targeting TRPV4-pyroptosis axis may represent a novel strategy to optimize orthodontic treatment efficiency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/00368504251409837","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T14:21:39Z","timestamp":1769091699000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Activation of TRPV4 to drive pyroptosis-dependent orthodontic tooth remodeling"],"prefix":"10.1177","volume":"109","author":[{"given":"Zhengquan","family":"He","sequence":"first","affiliation":[{"name":"Changsha Stomatological Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Tian","sequence":"additional","affiliation":[{"name":"Changsha Stomatological Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Changsha Stomatological Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yige","family":"Duan","sequence":"additional","affiliation":[{"name":"Changsha Stomatological Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengshan","family":"Chen","sequence":"additional","affiliation":[{"name":"Changsha Stomatological Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6379-004X","authenticated-orcid":false,"given":"Zhenyan","family":"Luo","sequence":"additional","affiliation":[{"name":"Changsha Stomatological Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12602"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-021-00125-5"},{"key":"e_1_3_4_4_2","first-page":"484","article-title":"Periodontal ligament reactions to orthodontic force: a transcriptomic study on maxillary and mandibular human premolars","volume":"60","author":"Zuodong Z","year":"2024","unstructured":"Zuodong Z, Mihai T, Maria G, et al. Periodontal ligament reactions to orthodontic force: a transcriptomic study on maxillary and mandibular human premolars. 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