{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T17:52:58Z","timestamp":1778003578009,"version":"3.51.4"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:p>\n                    Several studies have previously shown that histone deacetylase 4 (HDAC4) can regulate endoplasmic reticulum stress\u2010induced apoptosis through the activating transcription factor 4 (ATF4)\/CAAT\/enhancer binding protein homologous (CHOP) signaling pathway, thereby affecting the progression of osteoarthritis (OA). The present study investigated the regulatory mechanism of HDAC4 in chondrocyte apoptosis in OA using Acan\u2010Cre\n                    <jats:sup>ERT2<\/jats:sup>\n                    ;HDAC4\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    gene knockout mice. Forty mice were divided into four groups: TM\u2010DMM group [tamoxifen (TM) injection at 2\u2009months of age and destabilization of the medial meniscus (DMM) surgery at 3\u2009months], TM\u2010sham group (TM injection at 2\u2009months of age and sham surgery at 3\u2009months), no TM\u2010DMM group (corn oil injection at 2\u2009months of age and DMM surgery at 3\u2009months) and no TM\u2010sham group (corn oil injection at 2\u2009months of age and sham surgery at 3\u2009months). Apoptosis and cartilage damage were assessed through imaging, histological analysis, immunohistochemistry, reverse transcriptase\u2010PCR and terminal deoxynucleotidyl transferase\u2010mediated dUTP nick end labeling staining. HDAC4 knockdown resulted in increased osteophyte formation, significant narrowing of the joint space and increased articular cartilage damage. Furthermore, expression levels of key apoptosis\u2010related markers, ATF4, CHOP, caspase\u20103 and caspase\u20109, were significantly higher in the TM groups than in their respective control groups. Taken together, our results suggest that HDAC4 deficiency leads to increased apoptosis induced by the ATF4\/CHOP signaling pathway in the pathogenesis of OA. Therefore, upregulation of HDAC4 may represent a potential therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.13965","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T05:24:51Z","timestamp":1738560291000},"page":"726-737","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>HDAC4<\/scp>\n                    regulates apoptosis in Acan\u2010\n                    <scp>\n                      Cre\n                      <sup>ERT2<\/sup>\n                    <\/scp>\n                    ;\n                    <scp>\n                      HDAC4\n                      <sup>d<\/sup>\n                    <\/scp>\n                    <sup>\/d<\/sup>\n                    mice with osteoarthritis by downregulating\n                    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