{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:35:58Z","timestamp":1782815758441,"version":"3.54.5"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901137"],"award-info":[{"award-number":["81901137"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201575"],"award-info":[{"award-number":["82201575"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["Z2021086"],"award-info":[{"award-number":["Z2021086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["ZJGQNKJ202204"],"award-info":[{"award-number":["ZJGQNKJ202204"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017962","name":"Jiangsu Commission of Health","doi-asserted-by":"publisher","award":["81901137"],"award-info":[{"award-number":["81901137"]}],"id":[{"id":"10.13039\/100017962","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017962","name":"Jiangsu Commission of Health","doi-asserted-by":"publisher","award":["82201575"],"award-info":[{"award-number":["82201575"]}],"id":[{"id":"10.13039\/100017962","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017962","name":"Jiangsu Commission of Health","doi-asserted-by":"publisher","award":["Z2021086"],"award-info":[{"award-number":["Z2021086"]}],"id":[{"id":"10.13039\/100017962","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017962","name":"Jiangsu Commission of Health","doi-asserted-by":"publisher","award":["ZJGQNKJ202204"],"award-info":[{"award-number":["ZJGQNKJ202204"]}],"id":[{"id":"10.13039\/100017962","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Zhangjiagang Technology Project for Youth","award":["81901137"],"award-info":[{"award-number":["81901137"]}]},{"name":"Zhangjiagang Technology Project for Youth","award":["82201575"],"award-info":[{"award-number":["82201575"]}]},{"name":"Zhangjiagang Technology Project for Youth","award":["Z2021086"],"award-info":[{"award-number":["Z2021086"]}]},{"name":"Zhangjiagang Technology Project for Youth","award":["ZJGQNKJ202204"],"award-info":[{"award-number":["ZJGQNKJ202204"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for bone cancer pain. The pathological mechanism of chronic pain is increasingly being affected by epigenetic mechanisms. In this study, we unbiasedly showed that the DNA hydroxymethylase ten-eleven translocation 1 (TET1) expression was significantly increased in the L4\u20136 DRG of BCP rats and ten-eleven translocation 2 (TET2) expression did not change significantly. Notably, TET1 inhibition by intrathecal injection of Bobcat339 (a TET1 inhibitor) effectively relieved mechanical hyperalgesia in BCP rats. Peripheral sensitization in chronic pain relies on the activation and overexpression of ion channels on neurons. Here, we demonstrated that TRPV4, one of the transient receptor potential ion channel family members, was significantly elevated in the L4\u20136 DRG of BCP rats. In addition, TRPV4 inhibition by intrathecal injection of HC067047 (a TRPV4 inhibitor) also significantly attenuated mechanical hyperalgesia in BCP rats. Interestingly, we found that TET1 inhibition downregulated TRPV4 expression in the L4\u20136 DRG of BCP rats. As a result, these findings suggested that TET1 may contribute to bone cancer pain by upregulating TRPV4 expression in the L4\u20136 DRG of BCP rats and that TET1 or TRPV4 may become therapeutic targets for bone cancer pain.<\/jats:p>","DOI":"10.3390\/brainsci13040644","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T05:59:33Z","timestamp":1681106373000},"page":"644","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats"],"prefix":"10.3390","volume":"13","author":[{"given":"Zhen-Hua","family":"Xu","sequence":"first","affiliation":[{"name":"Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China"},{"name":"Department of Anesthesiology, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Niu","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China"},{"name":"Department of Anesthesiology, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-4327","authenticated-orcid":false,"given":"Xiao-Long","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Song","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8720-2734","authenticated-orcid":false,"given":"Hai-Long","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang 215600, China"},{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1002\/jbmr.3618","article-title":"Understanding the Bone in Cancer Metastasis","volume":"33","author":"Fornetti","year":"2018","journal-title":"J. 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