{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:53:16Z","timestamp":1789051996827,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T00:00:00Z","timestamp":1538006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec><jats:label\/><jats:p>Even though increasing evidence indicates the importance of peroxisomal lipid metabolism in regulating biological and pathological events, its involvement in cartilage development has not been well studied. Here, we identified the importance of peroxisomal function, particularly the functional integrity of ABCD2, in the pathogenesis of osteoarthritis (OA). Knockdown of ABCD2 in OA chondrocytes induced the accumulation of very long chain fatty acids (VLCFAs) and apoptotic cell death. Moreover, knockdown of ABCD2 altered profiles of miRNAs that affect the expression level of ACSL4, a known direct regulator of lipid metabolism. Suppression of ACSL4 in human chondrocytes\u2010induced VLCFA accumulation, MMP\u201013 expression, and apoptotic cell death. In vivo morph\u2010down of the ACSL4 homologue in zebrafish resulted in significant defects in cartilage development and in vivo knockdown of ACSL4 in cartilage tissue of an OA model mice promoted severe cartilage degradation. In summary, to the best of our knowledge, this is the first report suggesting that the regulatory network among peroxisomal ABCD2:ACSL4:VLCFA serves as a novel regulator of cartilage homeostasis, and these data may provide novel insights into the role of peroxisomal fatty acid metabolism in pathogenesis of human OA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance of the study<\/jats:title><jats:p>Our study indicates that peroxisomal dysfunction is closely related to OA pathogenesis. Particularly, the functional integrity of ABCD2 may play an important role in OA pathogenesis via the accumulation of VLCFAs and stimulation of apoptotic death through altering profiles of miRNAs that target ACSL4. Our findings suggest that targeting the regulatory network among the peroxisomal ABCD2:ACSL4:VLCFA axis may provide a new potential therapeutic strategy for OA pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cbf.3356","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T23:15:52Z","timestamp":1538090152000},"page":"366-376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Suppression of <scp>ABCD2<\/scp> dysregulates lipid metabolism via dysregulation of <scp>miR\u2010141:ACSL4<\/scp> in human osteoarthritis"],"prefix":"10.1002","volume":"36","author":[{"given":"Sujeong","family":"Park","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences Wonkwang University  Iksan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjoo","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of 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