{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:42:55Z","timestamp":1792698175678,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T00:00:00Z","timestamp":1693008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"KAKENHI","doi-asserted-by":"publisher","award":["21K10168"],"award-info":[{"award-number":["21K10168"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,18]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Orthodontic mechanical force on the periodontal ligament induces extracellular adenosine triphosphate (ATP) release. However, mechanosensitive molecules have not been confirmed functionally in periodontal ligament cells. In the present study, we examined the roles of mechanosensitive PIEZO channels in the mechanically stimulated release of ATP in human periodontal ligament fibroblasts (HPdLFs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>To examine PIEZO expression in HPdLFs, we performed reverse transcription\u2013quantitative polymerase chain reaction, fluorescent immunostaining, and Ca2+ imaging. ATP concentrations were measured in culture medium after applications of the PIEZO1 agonist Yoda1 and compression force in a newly developed in vitro weight-loaded cell model (IVWLC) using balance weights and a 48-well plate. The mechanosensitive channel inhibitor GsMTx4 and the ATP-releasing route inhibitors clodronic acid, meclofenamic acid, and probenecid were used. To suppress PIEZO1 expression, short interference RNA (siRNA) treatment of the PIEZO1 gene was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PIEZO1 mRNA was expressed more abundantly than PIEZO2 mRNA in HPdLFs. HPdLF cell bodies were immunoreactive to anti-PIEZO1 antibody. Yoda1 increased intracellular Ca2+ and extracellular ATP concentrations in a dose-dependent manner. ATP release was inhibited by GsMTx4 and inhibitors of ATP release routes. In the IVWLC, HPdLFs released ATP in response to compression force but not in response to hypoxic stimulation that was simultaneously applied to cells. Mechanically stimulated ATP release was inhibited by GsMTx4, inhibitors of ATP-releasing routes and siRNA treatment of PIEZO1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PIEZO1 on the cell membranes of HPdLFs is activated by compression force and then induces ATP release via intracellular Ca2+-dependent exocytosis and ATP-permeable channels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejo\/cjad052","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T11:32:46Z","timestamp":1692271966000},"page":"565-574","source":"Crossref","is-referenced-by-count":17,"title":["PIEZO1 promotes ATP release from periodontal ligament cells following compression force"],"prefix":"10.1093","volume":"45","author":[{"given":"Seiwa","family":"Horie","sequence":"first","affiliation":[{"name":"Division of Physiology, Kyushu Dental University , 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responses and expression of P2X3 receptor in trigeminal ganglion after experimental tooth movement in rats","volume-title":"Arch Oral Biol","author":"Yang","year":"2009"},{"key":"2023091805150194500_CIT0005","first-page":"69","article-title":"Purinergic mechanosensory transduction and visceral pain","volume-title":"Mol Pain","author":"Burnstock","year":"2009"},{"key":"2023091805150194500_CIT0006","first-page":"404","article-title":"Adenosine triphosphate stimulates RANKL expression through P2Y1 receptor-cyclo-oxygenase-dependent pathway in human periodontal ligament cells","volume-title":"J Periodontal Res","author":"Luckprom","year":"2010"},{"key":"2023091805150194500_CIT0007","first-page":"564","article-title":"Mechanical stress induces osteopontin via ATP\/P2Y1 in periodontal cells","volume-title":"J Dent Res","author":"Wongkhantee","year":"2008"},{"key":"2023091805150194500_CIT0008","first-page":"169","article-title":"Mechanical stress-induced interleukin-1beta expression through adenosine triphosphate\/P2X7 receptor activation in human periodontal ligament cells","volume-title":"J Periodontal Res","author":"Kanjanamekanant","year":"2013"},{"key":"2023091805150194500_CIT0009","first-page":"104607","article-title":"Vesicular nucleotide transporter mediates adenosine triphosphate release in compressed human periodontal ligament fibroblast cells and participates in tooth movement-induced nociception in rats","volume-title":"Arch Oral Biol","author":"Mizuhara","year":"2020"},{"key":"2023091805150194500_CIT0010","first-page":"595","article-title":"P2X7 receptor-Pannexin1 interaction mediates stress-induced interleukin-1 beta expression in human periodontal ligament cells","volume-title":"J Periodontal Res","author":"Kanjanamekanant","year":"2014"},{"key":"2023091805150194500_CIT0011","first-page":"607","article-title":"Role of connexin43 hemichannels in mechanical stress-induced ATP release in human periodontal ligament cells","volume-title":"J Periodontal 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osteoarthritis pain","volume-title":"Front Cell Dev Biol","author":"Emmi","year":"2022"},{"key":"2023091805150194500_CIT0027","first-page":"210","article-title":"Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor kappaB ligand up-regulation via prostaglandin E2 synthesis","volume-title":"J Bone Miner Res","author":"Kanzaki","year":"2002"},{"key":"2023091805150194500_CIT0028","first-page":"87","article-title":"Functional role of mechanosensitive ion channel Piezo1 in human periodontal ligament cells","volume-title":"Angle Orthod","author":"Jin","year":"2015"},{"key":"2023091805150194500_CIT0029","first-page":"33","article-title":"The role of mechanotransduction versus hypoxia during simulated orthodontic compressive strain-an in vitro study of human periodontal ligament fibroblasts","volume-title":"Int J Oral 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