{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:25:57Z","timestamp":1786951557017,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803179"],"award-info":[{"award-number":["81803179"]}],"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":["82273752"],"award-info":[{"award-number":["82273752"]}],"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":["82373700"],"award-info":[{"award-number":["82373700"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Kashin\u2010Beck disease (KBD) is a chronic, endemic osteoarticular disorder associated with T\u20102 toxin exposure, which is rapidly metabolized to HT\u20102 toxin in vivo. However, the role of zinc transporter\n                    <jats:italic>ZIP6<\/jats:italic>\n                    in HT\u20102 toxin\u2010induced extracellular matrix metabolic disturbance in chondrocytes remains unclear. This study established HT\u20102 toxin intervention and\n                    <jats:italic>ZIP6<\/jats:italic>\n                    knockdown chondrocyte models, combined with quantitative reverse transcription polymerase chain reaction (qRT\u2010PCR) and transcriptome sequencing, to investigate the regulatory mechanisms of\n                    <jats:italic>ZIP6<\/jats:italic>\n                    in chondrocyte injury. Following HT\u20102 toxin exposure, altered chondrocyte morphology and reduced cell viability were observed;\n                    <jats:italic>ZIP6<\/jats:italic>\n                    ,\n                    <jats:italic>COL2A1<\/jats:italic>\n                    ,\n                    <jats:italic>MTF1<\/jats:italic>\n                    , and\n                    <jats:italic>MTF2<\/jats:italic>\n                    expression were significantly downregulated, whereas\n                    <jats:italic>MMP1<\/jats:italic>\n                    ,\n                    <jats:italic>MMP13<\/jats:italic>\n                    , and\n                    <jats:italic>COL10A1<\/jats:italic>\n                    were upregulated.\n                    <jats:italic>ZIP6<\/jats:italic>\n                    knockdown significantly upregulated\n                    <jats:italic>COL2A1<\/jats:italic>\n                    ,\n                    <jats:italic>MTF1<\/jats:italic>\n                    , and\n                    <jats:italic>MTF2<\/jats:italic>\n                    , downregulated\n                    <jats:italic>MMP1<\/jats:italic>\n                    and\n                    <jats:italic>COL10A1<\/jats:italic>\n                    , but did not alter\n                    <jats:italic>MMP13<\/jats:italic>\n                    expression. Differentially expressed genes following\n                    <jats:italic>ZIP6<\/jats:italic>\n                    knockdown were predominantly enriched in FoxO, cAMP, and TNF signaling pathways. qRT\u2010PCR validation confirmed consistent expression changes in\n                    <jats:italic>FOXO4<\/jats:italic>\n                    ,\n                    <jats:italic>TNFSF10<\/jats:italic>\n                    ,\n                    <jats:italic>COLEC10<\/jats:italic>\n                    ,\n                    <jats:italic>UCA1<\/jats:italic>\n                    , and\n                    <jats:italic>LRRC17<\/jats:italic>\n                    with transcriptome sequencing results. Collectively, HT\u20102 toxin suppresses\n                    <jats:italic>ZIP6<\/jats:italic>\n                    ,\n                    <jats:italic>MTF1<\/jats:italic>\n                    , and\n                    <jats:italic>MTF2<\/jats:italic>\n                    expression, disrupting chondrocyte extracellular matrix metabolism; conversely,\n                    <jats:italic>ZIP6<\/jats:italic>\n                    knockdown ameliorates matrix metabolic abnormalities through modulation of relevant signaling pathways. These findings reveal differential regulatory effects of HT\u20102 toxin and\n                    <jats:italic>ZIP6<\/jats:italic>\n                    on cartilage matrix metabolism, providing experimental evidence for elucidating molecular mechanisms underlying cartilage injury\u2010related diseases.\n                  <\/jats:p>","DOI":"10.1002\/jbt.71056","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:53:27Z","timestamp":1785473607000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Contrasting Effects of HT\u20102 Toxin Exposure and\n                    <i>ZIP6<\/i>\n                    Knockdown on Chondrocyte Extracellular Matrix Metabolism"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7372-0118","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Occupational and Environmental Health School of Public Health, Health Science Center, Xi'an Jiaotong University Xi'an Shaanxi P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health School of Public Health, Health Science Center, Xi'an Jiaotong University Xi'an Shaanxi P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruitian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health School of Public Health, Health Science Center, Xi'an Jiaotong University Xi'an Shaanxi P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health School of Public Health, Health Science Center, Xi'an Jiaotong University Xi'an Shaanxi P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6951-7277","authenticated-orcid":false,"given":"Lian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health School of Public Health, Health Science Center, Xi'an Jiaotong University Xi'an Shaanxi P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaowei","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission School of Public Health, Health Science Center\uff0cXi'an Jiaotong University Xi'an Shaanxi P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yirong","family":"Qin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission School of Public Health, Health Science Center\uff0cXi'an Jiaotong University Xi'an Shaanxi P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission School of Public Health, Health Science Center\uff0cXi'an Jiaotong University Xi'an Shaanxi P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission School of Public Health, Health Science Center\uff0cXi'an Jiaotong University Xi'an Shaanxi P.R. China"},{"name":"Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, School of Public Health, Health Science Center Xi'an Jiaotong University Xi'an Shaanxi P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Occupational and Environmental Health School of Public Health, Health Science Center, Xi'an Jiaotong University Xi'an Shaanxi P.R. 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