{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:12:21Z","timestamp":1789053141506,"version":"build-2803163510"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000072","name":"U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE32530"],"award-info":[{"award-number":["DE32530"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE32530"],"award-info":[{"award-number":["DE32530"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Oral Sci"],"DOI":"10.1038\/s41368-026-00461-4","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:49:36Z","timestamp":1789008576000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Piezo channels contribute to the terminal cytodifferentiation of odontoblasts via modulation of canonical Wnt signaling"],"prefix":"10.1038","volume":"18","author":[{"given":"Xuguang","family":"Nie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5061-4266","authenticated-orcid":false,"given":"Kelley","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Kyo","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"461_CR1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1126\/science.1193270","volume":"330","author":"B Coste","year":"2010","unstructured":"Coste, B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330, 55\u201360 (2010).","journal-title":"Science"},{"key":"461_CR2","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/nature10801","volume":"483","author":"SE Kim","year":"2012","unstructured":"Kim, S. E., Coste, B., Chadha, A., Cook, B. & Patapoutian, A. The role of Drosophila Piezo in mechanical nociception. Nature 483, 209\u2013212 (2012).","journal-title":"Nature"},{"key":"461_CR3","doi-asserted-by":"publisher","first-page":"31673","DOI":"10.1074\/jbc.R114.612697","volume":"289","author":"SN Bagriantsev","year":"2014","unstructured":"Bagriantsev, S. N., Gracheva, E. O. & Gallagher, P. G. Piezo proteins: regulators of mechanosensation and other cellular processes. J. Biol. Chem. 289, 31673\u201331681 (2014).","journal-title":"J. Biol. Chem."},{"key":"461_CR4","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.diff.2022.06.001","volume":"126","author":"X Nie","year":"2022","unstructured":"Nie, X. & Chung, M. K. Piezo channels for skeletal development and homeostasis: insights from mouse genetic models. Differentiation 126, 10\u201315 (2022).","journal-title":"Differentiation"},{"key":"461_CR5","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s00424-014-1578-z","volume":"467","author":"L Volkers","year":"2015","unstructured":"Volkers, L., Mechioukhi, Y. & Coste, B. Piezo channels: from structure to function. Pflug. Arch. 467, 95\u201399 (2015).","journal-title":"Pflug. Arch."},{"key":"461_CR6","doi-asserted-by":"crossref","unstructured":"Nie, X., Abbasi, Y. & Chung, M. K. Piezo1 and Piezo2 collectively regulate jawbone development. Development 151, dev202386 (2024).","DOI":"10.1242\/dev.202386"},{"key":"461_CR7","doi-asserted-by":"crossref","unstructured":"Canales Couti\u00f1o, B. & Mayor, R. The mechanosensitive channel Piezo1 cooperates with semaphorins to control neural crest migration. Development 148, dev200001 (2021).","DOI":"10.1242\/dev.200001"},{"key":"461_CR8","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1038\/nn.4162","volume":"18","author":"SH Woo","year":"2015","unstructured":"Woo, S. H. et al. Piezo2 is the principal mechanotransduction channel for proprioception. Nat. Neurosci. 18, 1756\u20131762 (2015).","journal-title":"Nat. Neurosci."},{"key":"461_CR9","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/nature20793","volume":"541","author":"K Nonomura","year":"2017","unstructured":"Nonomura, K. et al. Piezo2 senses airway stretch and mediates lung inflation-induced apnoea. Nature 541, 176\u2013181 (2017).","journal-title":"Nature"},{"key":"461_CR10","doi-asserted-by":"publisher","first-page":"10347","DOI":"10.1073\/pnas.1409233111","volume":"111","author":"SS Ranade","year":"2014","unstructured":"Ranade, S. S. et al. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc. Natl. Acad. Sci. USA 111, 10347\u201310352 (2014).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"461_CR11","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1002\/jbmr.4198","volume":"36","author":"G Hendrickx","year":"2020","unstructured":"Hendrickx, G. et al. Piezo1 inactivation in chondrocytes impairs trabecular bone formation. J. Bone Min. Res 36, 369\u2013384 (2020).","journal-title":"J. Bone Min. Res"},{"key":"461_CR12","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1177\/00220345251317429","volume":"104","author":"S Wang","year":"2025","unstructured":"Wang, S. et al. Nociceptor neurons facilitate orthodontic tooth movement via Piezo2 in mice. J. Dent. Res. 104, 890\u2013899 (2025).","journal-title":"J. Dent. Res."},{"key":"461_CR13","doi-asserted-by":"crossref","unstructured":"Zhou, T. et al. Piezo1\/2 mediate mechanotransduction essential for bone formation through concerted activation of NFAT-YAP1-ss-catenin. eLife 9, e52779 (2020).","DOI":"10.7554\/eLife.52779"},{"key":"461_CR14","doi-asserted-by":"crossref","unstructured":"Sun, W. et al. The mechanosensitive Piezo1 channel is required for bone formation. eLife 8, e47454 (2019).","DOI":"10.7554\/eLife.47454"},{"key":"461_CR15","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41413-021-00168-8","volume":"9","author":"L Qin","year":"2021","unstructured":"Qin, L. et al. Roles of mechanosensitive channel Piezo1\/2 proteins in skeleton and other tissues. Bone Res. 9, 44 (2021).","journal-title":"Bone Res."},{"key":"461_CR16","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/eos.12421","volume":"126","author":"I Thesleff","year":"2018","unstructured":"Thesleff, I. From understanding tooth development to bioengineering of teeth. Eur. J. Oral. Sci. 126, 67\u201371 (2018).","journal-title":"Eur. J. Oral. Sci."},{"key":"461_CR17","doi-asserted-by":"crossref","unstructured":"Yu, T. & Klein, O. D. Molecular and cellular mechanisms of tooth development, homeostasis and repair. Development 147, dev184754 (2020).","DOI":"10.1242\/dev.184754"},{"key":"461_CR18","doi-asserted-by":"publisher","first-page":"e1800140","DOI":"10.1002\/bies.201800140","volume":"40","author":"ZT Calamari","year":"2018","unstructured":"Calamari, Z. T., Hu, J. K. H. & Klein, O. D. Tissue mechanical forces and evolutionary developmental changes act through space and time to shape tooth morphology and function. Bioessays 40, e1800140 (2018).","journal-title":"Bioessays"},{"key":"461_CR19","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1002\/ar.25351","volume":"307","author":"JJ Gaite","year":"2024","unstructured":"Gaite, J. J. et al. Immunolocalization of the mechanogated ion channels PIEZO1 and PIEZO2 in human and mouse dental pulp and periodontal ligament. Anat. Rec. 307, 1960\u20131968 (2024).","journal-title":"Anat. Rec."},{"key":"461_CR20","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.891759","volume":"13","author":"S Ohyama","year":"2022","unstructured":"Ohyama, S. et al. Piezo1-pannexin-1-P2X(3) axis in odontoblasts and neurons mediates sensory transduction in dentinal sensitivity. Front. Physiol. 13, 891759 (2022).","journal-title":"Front. Physiol."},{"key":"461_CR21","doi-asserted-by":"publisher","first-page":"e1007491","DOI":"10.1371\/journal.pgen.1007491","volume":"14","author":"X Nie","year":"2018","unstructured":"Nie, X. et al. mTOR acts as a pivotal signaling hub for neural crest cells during craniofacial development. PLoS Genet. 14, e1007491 (2018).","journal-title":"PLoS Genet."},{"key":"461_CR22","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1111\/j.1432-0436.2006.00150.x","volume":"75","author":"T Yamashiro","year":"2007","unstructured":"Yamashiro, T. et al. Wnt10a regulates dentin sialophosphoprotein mRNA expression and possibly links odontoblast differentiation and tooth morphogenesis. Differentiation 75, 452\u2013462 (2007).","journal-title":"Differentiation"},{"key":"461_CR23","doi-asserted-by":"publisher","first-page":"100838","DOI":"10.1016\/j.diff.2025.100838","volume":"142","author":"EL Benard","year":"2025","unstructured":"Benard, E. L. & Hammerschmidt, M. The fundamentals of WNT10A. Differentiation 142, 100838 (2025).","journal-title":"Differentiation"},{"key":"461_CR24","doi-asserted-by":"publisher","first-page":"340","DOI":"10.3390\/genes14020340","volume":"14","author":"K Yoshinaga","year":"2023","unstructured":"Yoshinaga, K. et al. Effects of Wnt10a and Wnt10b double mutations on tooth development. Genes 14, 340 (2023).","journal-title":"Genes"},{"key":"461_CR25","doi-asserted-by":"crossref","unstructured":"Shull, L. C. et al. PRDM paralogs antagonistically balance Wnt\/beta-catenin activity during craniofacial chondrocyte differentiation. Development 149, dev200082(2022).","DOI":"10.1242\/dev.200082"},{"key":"461_CR26","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1128\/MCB.22.4.1172-1183.2002","volume":"22","author":"E Jho","year":"2002","unstructured":"Jho, E. et al. Wnt\/beta-catenin\/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol. Cell Biol. 22, 1172\u20131183 (2002).","journal-title":"Mol. Cell Biol."},{"key":"461_CR27","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1086\/386293","volume":"74","author":"L Lammi","year":"2004","unstructured":"Lammi, L. et al. Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am. J. Hum. Genet. 74, 1043\u20131050 (2004).","journal-title":"Am. J. Hum. Genet."},{"key":"461_CR28","doi-asserted-by":"publisher","first-page":"1039714","DOI":"10.3389\/fphys.2022.1039714","volume":"13","author":"Y Lin","year":"2022","unstructured":"Lin, Y., Ren, J. & McGrath, C. Mechanosensitive Piezo1 and Piezo2 ion channels in craniofacial development and dentistry: Recent advances and prospects. Front. Physiol. 13, 1039714 (2022).","journal-title":"Front. Physiol."},{"key":"461_CR29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2504103122","volume":"122","author":"L Meng","year":"2025","unstructured":"Meng, L. et al. Piezo2+ mechanosensory neurons orchestrate postnatal development through mechano-chemo-transduction of PDGFA signaling. Proc. Natl. Acad. Sci. USA 122, e2504103122 (2025).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"461_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-36699-9","volume":"13","author":"C Nottmeier","year":"2023","unstructured":"Nottmeier, C. et al. Mechanical-induced bone remodeling does not depend on Piezo1 in dentoalveolar hard tissue. Sci. Rep. 13, 9563 (2023).","journal-title":"Sci. Rep."},{"key":"461_CR31","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41368-025-00374-8","volume":"17","author":"PR Lee","year":"2025","unstructured":"Lee, P. R., Lee, K., Park, J. M., Kim, S. & Oh, S. B. Functional and distinct roles of Piezo2-mediated mechanotransduction in dental primary afferent neurons. Int. J. Oral. Sci. 17, 45 (2025).","journal-title":"Int. J. Oral. Sci."},{"key":"461_CR32","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.945948","volume":"16","author":"YS Cho","year":"2022","unstructured":"Cho, Y. S. et al. Expression of Piezo1 in the trigeminal neurons and in the axons that innervate the dental pulp. Front. Cell Neurosci. 16, 945948 (2022).","journal-title":"Front. Cell Neurosci."},{"key":"461_CR33","doi-asserted-by":"publisher","first-page":"E5114","DOI":"10.1073\/pnas.1414298111","volume":"111","author":"W Lee","year":"2014","unstructured":"Lee, W. et al. Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage. Proc. Natl. Acad. Sci. USA 111, E5114\u2013E5122 (2014).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"461_CR34","doi-asserted-by":"crossref","unstructured":"Dalghi, M. G. et al. Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception. JCI Insight 6, e152984(2021).","DOI":"10.1172\/jci.insight.152984"},{"key":"461_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109877","volume":"78","author":"F Pei","year":"2021","unstructured":"Pei, F. et al. The functions of mechanosensitive ion channels in tooth and bone tissues. Cell Signal. 78, 109877 (2021).","journal-title":"Cell Signal."},{"key":"461_CR36","doi-asserted-by":"publisher","first-page":"5250","DOI":"10.3390\/ijms23095250","volume":"23","author":"Y Zhou","year":"2022","unstructured":"Zhou, Y., Zhang, C., Zhou, Z., Zhang, C. & Wang, J. Identification of key genes and pathways associated with PIEZO1 in bone-related disease based on bioinformatics. Int. J. Mol. Sci. 23, 5250 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"461_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-51381-9","volume":"9","author":"A Miyazaki","year":"2019","unstructured":"Miyazaki, A. et al. Coordination of WNT signaling and ciliogenesis during odontogenesis by piezo type mechanosensitive ion channel component 1. Sci. Rep. 9, 14762 (2019).","journal-title":"Sci. Rep."},{"key":"461_CR38","doi-asserted-by":"publisher","first-page":"31368","DOI":"10.1021\/acsomega.5c00284","volume":"10","author":"B Tan","year":"2025","unstructured":"Tan, B. et al. The critical role of Piezo1\/CaMKII\/beta-catenin axis in promoting osteogenic differentiation of ADSCs by pressure stimulation. ACS Omega 10, 31368\u201331380 (2025).","journal-title":"ACS Omega"},{"key":"461_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06466-3","volume":"15","author":"J He","year":"2024","unstructured":"He, J., Cheng, X., Fang, B., Shan, S. & Li, Q. Mechanical stiffness promotes skin fibrosis via Piezo1-Wnt2\/Wnt11-CCL24 positive feedback loop. Cell Death Dis. 15, 84 (2024).","journal-title":"Cell Death Dis."},{"key":"461_CR40","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.ydbio.2009.07.015","volume":"334","author":"J Chen","year":"2009","unstructured":"Chen, J., Lan, Y., Baek, J. A., Gao, Y. & Jiang, R. Wnt\/beta-catenin signaling plays an essential role in activation of odontogenic mesenchyme during early tooth development. Dev. Biol. 334, 174\u2013185 (2009).","journal-title":"Dev. Biol."},{"key":"461_CR41","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1316635","volume":"14","author":"R Raju","year":"2023","unstructured":"Raju, R. et al. Profiles of Wnt pathway gene expression during tooth morphogenesis. Front. Physiol. 14, 1316635 (2023).","journal-title":"Front. Physiol."},{"key":"461_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15397","volume":"8","author":"M Xu","year":"2017","unstructured":"Xu, M. et al. WNT10A mutation causes ectodermal dysplasia by impairing progenitor cell proliferation and KLF4-mediated differentiation. Nat. Commun. 8, 15397 (2017).","journal-title":"Nat. Commun."},{"key":"461_CR43","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1111\/boc.201100075","volume":"104","author":"M Aurrekoetxea","year":"2012","unstructured":"Aurrekoetxea, M., Lopez, J., Garc\u00eda, P., Ibarretxe, G. & Unda, F. Enhanced Wnt\/beta-catenin signalling during tooth morphogenesis impedes cell differentiation and leads to alterations in the structure and mineralisation of the adult tooth. Biol. Cell 104, 603\u2013617 (2012).","journal-title":"Biol. Cell"},{"key":"461_CR44","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/bs.ctm.2017.01.001","volume":"79","author":"SL Alper","year":"2017","unstructured":"Alper, S. L. Genetic diseases of PIEZO1 and PIEZO2 dysfunction. Curr. Top. Membr. 79, 97\u2013134 (2017).","journal-title":"Curr. Top. Membr."},{"key":"461_CR45","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1146\/annurev-neuro-093020-120939","volume":"44","author":"R Syeda","year":"2021","unstructured":"Syeda, R. Physiology and pathophysiology of mechanically activated PIEZO channels. Annu. Rev. Neurosci. 44, 383\u2013402 (2021).","journal-title":"Annu. Rev. Neurosci."},{"key":"461_CR46","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.ydbio.2013.04.026","volume":"379","author":"AE Lewis","year":"2013","unstructured":"Lewis, A. E., Vasudevan, H. N., O\u2019Neill, A. K., Soriano, P. & Bush, J. O. The widely used Wnt1-Cre transgene causes developmental phenotypes by ectopic activation of Wnt signaling. Dev. Biol. 379, 229\u2013234 (2013).","journal-title":"Dev. Biol."},{"key":"461_CR47","doi-asserted-by":"crossref","unstructured":"Cahalan, S. M. et al. Piezo1 links mechanical forces to red blood cell volume. eLife 4, (2015).","DOI":"10.7554\/eLife.07370"},{"key":"461_CR48","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/nature13251","volume":"509","author":"SH Woo","year":"2014","unstructured":"Woo, S. H. et al. Piezo2 is required for Merkel-cell mechanotransduction. Nature 509, 622\u2013626 (2014).","journal-title":"Nature"},{"key":"461_CR49","doi-asserted-by":"crossref","unstructured":"Matrongolo, M. J. et al. Piezo1 agonist restores meningeal lymphatic vessels, drainage, and brain-CSF perfusion in craniosynostosis and aged mice. J. Clin. Investig. 134, e171468 (2024).","DOI":"10.1172\/JCI171468"}],"container-title":["International Journal of Oral Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41368-026-00461-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41368-026-00461-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41368-026-00461-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:03:12Z","timestamp":1789052592000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41368-026-00461-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["461"],"URL":"https:\/\/doi.org\/10.1038\/s41368-026-00461-4","relation":{},"ISSN":["2049-3169"],"issn-type":[{"value":"2049-3169","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]},"assertion":[{"value":"18 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 July 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"61"}}