{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:35:36Z","timestamp":1784734536128,"version":"3.55.0"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K12307"],"award-info":[{"award-number":["24K12307"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008731","name":"Nakatomi Foundation","doi-asserted-by":"publisher","award":["7102200377"],"award-info":[{"award-number":["7102200377"]}],"id":[{"id":"10.13039\/100008731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007428","name":"Naito Foundation","doi-asserted-by":"publisher","award":["7102300454"],"award-info":[{"award-number":["7102300454"]}],"id":[{"id":"10.13039\/100007428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2026,3]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objective<\/jats:title>\n \n Major cause of low\u2010back pain is intervertebral disc degeneration (\n IVDD<\/jats:styled-content>\n ), with mechanical stress playing a crucial role in its progression. A mechanosensitive ion channel,\n PIEZO1<\/jats:styled-content>\n , is involved in various musculoskeletal tissues, but its role in the annulus fibrosus (\n AF<\/jats:styled-content>\n ) remains unclear. This study aimed to elucidate the function of\n PIEZO1<\/jats:styled-content>\n in\n AF<\/jats:styled-content>\n cells under mechanical stimulation.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Primary rat\n AF<\/jats:styled-content>\n cells were subjected to cyclic tensile strain (\n CTS<\/jats:styled-content>\n ) at low (2%) and high (12%) strain levels to investigate strain\u2010dependent effects on osteogenic gene expression. We evaluated the effects of\n Piezo1<\/jats:italic>\n ,\n Piezo2<\/jats:italic>\n , and\n Trpv4<\/jats:italic>\n knockdown by\n RNA<\/jats:styled-content>\n interference to identify the upstream mechanotransducer. Furthermore,\n PIEZO1<\/jats:styled-content>\n was activated using the agonist Yoda1, followed by\n RNA<\/jats:styled-content>\n \u2010sequencing analysis and evaluation of its effects on\n BMP2<\/jats:styled-content>\n \u2010induced osteogenesis in rat\n AF<\/jats:styled-content>\n cells. We also examined the effects of Yoda1 in primary human\n AF<\/jats:styled-content>\n cells.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Low\u2010strain\n CTS<\/jats:styled-content>\n significantly suppressed osteogenic marker expression, which was not observed with high strain.\n Piezo1<\/jats:italic>\n knockdown reversed this suppression, whereas\n Piezo2<\/jats:italic>\n and\n Trpv4<\/jats:italic>\n had no effect. Piezo1 activation by Yoda1 produced similar anti\u2010osteogenic effects in both rat and human\n AF<\/jats:styled-content>\n cells.\n RNA<\/jats:styled-content>\n sequencing revealed the enrichment of ossification and calcineurin signaling pathways in rat cells. Furthermore, Piezo1 activation inhibited\n BMP2<\/jats:styled-content>\n \u2010induced osteogenesis and nuclear translocation of p\u2010Smad1\/5\/9.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Piezo1 maintains\n AF<\/jats:styled-content>\n cell homeostasis under mechanical stress by suppressing osteogenic changes via calcineurin\u2010mediated inhibition of\n BMP<\/jats:styled-content>\n signaling, which may represent a novel therapeutic target for\n IVDD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jsp2.70168","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T09:04:40Z","timestamp":1772960680000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanosensitive Ion Channel\n PIEZO1<\/scp>\n Suppresses\n BMP2<\/scp>\n \u2010Induced Ossification of the Annulus Fibrosus Cells"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4710-7213","authenticated-orcid":false,"given":"Hisakazu","family":"Shitozawa","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0145-2135","authenticated-orcid":false,"given":"Ryo","family":"Nakamichi","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Graduate School Medicine, Dentistry, and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4790-933X","authenticated-orcid":false,"given":"Aki","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8726-7741","authenticated-orcid":false,"given":"Masataka","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1448-3202","authenticated-orcid":false,"given":"Taichi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Hospital Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5594-1292","authenticated-orcid":false,"given":"Koji","family":"Uotani","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Okayama University Hospital Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4608-6677","authenticated-orcid":false,"given":"Yoshiaki","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9488-2057","authenticated-orcid":false,"given":"Ryo","family":"Takatori","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3534-5506","authenticated-orcid":false,"given":"Kazutaka","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1732-9307","authenticated-orcid":false,"given":"Toshifumi","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(99)00187-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar629"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-200604002-00003"},{"key":"e_1_2_11_5_1","first-page":"43","article-title":"Identification of Heterogeneous Cell Populations in Normal Human Intervertebral Disc","volume":"186","author":"Chelberg M. K.","year":"1995","journal-title":"Journal of Anatomy"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13964"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00331"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"e0144497","DOI":"10.1371\/journal.pone.0144497","article-title":"Novel Immortal Cell Lines Support Cellular Heterogeneity in the Human Annulus Fibrosus","volume":"11","author":"Akker G. G.","year":"2016","journal-title":"PLoS One"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200212010-00002"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199506000-00022"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0720-048X(97)00165-4"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2302011842"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2016.03.026"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11162600"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096519"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2005.05.011"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2021.03.002"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-012-2371-3"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103601"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000146049.52152.da"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1529-9430(03)00174-8"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63179-3"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.11.022"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3229"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/PHM.0b013e31816197ee"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.57774"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2010.09.053"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-070918-050509"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6645193"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-022-02804-y"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8884922"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12503"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-019-0085-4"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2929"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj5557"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-023-03093-9"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022111799"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100050306"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep15662"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.015"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20081900"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-025-01147-z"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14440"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-023-03093-9"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21232"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mechmat.2011.07.016"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1026"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10608"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v022a11"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202201388R"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2024.04.001"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00544.2022"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14146-6"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2022.03.119"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126616"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18089-0"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.2929"}],"container-title":["JOR SPINE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jsp2.70168","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jsp2.70168","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jsp2.70168","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T11:24:18Z","timestamp":1774351458000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jsp2.70168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":56,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/jsp2.70168"],"URL":"https:\/\/doi.org\/10.1002\/jsp2.70168","archive":["Portico"],"relation":{},"ISSN":["2572-1143","2572-1143"],"issn-type":[{"value":"2572-1143","type":"print"},{"value":"2572-1143","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2025-08-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70168"}}