{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T09:00:49Z","timestamp":1781168449903,"version":"3.54.1"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This study aimed to investigate the role of the HDAC4 gene in the pathogenesis of Kashin\u2013Beck disease (KBD) cartilage injury and chondrocyte differentiation induced by T\u20102 toxin. Immunohistochemistry was used to compare HDAC4 and PTHrP protein expression levels in cartilage from children and adults who have KBD and from respective controls, as well as in cartilage from a rat model exposed to T\u20102 toxin and selenium deficiency. A KBD cell model was established by exposure to T\u20102 toxin, and RNA interference was employed to silence HDAC4. Expression levels of mRNA and protein expression levels were subsequently measured before and after HDAC4 gene silencing for genes related to the PTHrP\u2013HDAC4 signaling pathway and cartilage differentiation by real\u2010time quantitative reverse transcription PCR and western blotting. We found that HDAC4 expression levels were not consistent between adult and child chondrocytes. Silencing of HDAC4 resulted in a significant increase in the mRNA expression of Runx2 and PTHrP, and elevated the levels of both the mRNA and protein of MMP13, and increased both the mRNA and protein levels of MEF2C. Notably, following the addition of T\u20102 toxin, there was a significant increase in Runx2 expression, whereas the levels of MEF2C and MMP13 were markedly decreased in comparison to pre\u2010silencing conditions. These findings indicate that T\u20102 toxin may influence HDAC4 expression, and the role and regulatory mechanisms of this gene in impairing the differentiation of KBD chondrocytes were explored, thereby offering novel insights into the pathogenesis of KBD.<\/jats:p>","DOI":"10.1002\/jbt.70231","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T19:12:50Z","timestamp":1743275570000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the Role and Regulatory Mechanisms of the Histone Deacetylase 4 Gene in Chondrocyte Differentiation Impairments Associated With Kashin\u2013Beck Disease"],"prefix":"10.1002","volume":"39","author":[{"given":"Lei","family":"Yang","sequence":"first","affiliation":[{"name":"School of Nursing, Health Science Center Xi'an Jiaotong University Xi'an Shaanxi PR China"},{"name":"Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center Xi'an Jiaotong University Xi'an Shaanxi PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9351-600X","authenticated-orcid":false,"given":"Chaowei","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center Xi'an Jiaotong University Xi'an Shaanxi PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Nursing, Health Science Center Xi'an Jiaotong University Xi'an Shaanxi PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feihong","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center Xi'an Jiaotong University Xi'an Shaanxi PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center Xi'an Jiaotong University Xi'an Shaanxi PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center Xi'an Jiaotong University Xi'an Shaanxi PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2022.107255"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins15080481"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins11080471"},{"key":"e_1_2_11_5_1","first-page":"213","article-title":"Research Progress on T\u20102 Toxin and Its Relationship With Kashin\u2010Beck Disease","volume":"19","author":"Chen J.","year":"2004","journal-title":"Chinese Journal of Endemiology (in Chinese)"},{"key":"e_1_2_11_6_1","first-page":"1002","article-title":"Investigation Report on the Environmental and Disease Influencing Factors of Kashin\u2010Beck Disease Inside and Outside Historical Severe\u2010Affected Areas in Tibet","volume":"36","author":"Zhao S.","year":"2020","journal-title":"Journal of Medical Pest Control (in 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