{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:01:45Z","timestamp":1791932505272,"version":"4.3.4"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1I1A1A01041827"],"award-info":[{"award-number":["2019R1I1A1A01041827"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Since mitochondria are suggested to be important regulators in maintaining cartilage homeostasis, turnover of mitochondria through mitochondrial biogenesis and mitochondrial degradation may play an important role in the pathogenesis of osteoarthritis (OA). Here, we found that mitochondrial dysfunction is closely associated with OA pathogenesis and identified the peroxisome proliferator-activated receptor-gamma co-activator 1-alpha (PGC1\u03b1) as a potent regulator. The expression level of PGC1\u03b1 was significantly decreased under OA conditions, and knockdown of PGC1\u03b1 dramatically elevated the cartilage degradation by upregulating cartilage degrading enzymes and apoptotic cell death. Interestingly, the knockdown of PGC1\u03b1 activated the parkin RBR E3 ubiquitin protein ligase (PRKN)-independent selective mitochondria autophagy (mitophagy) pathway through the upregulation of BCL2 and adenovirus E1B 19-kDa-interacting protein 3 (BNIP3). The overexpression of BNIP3 stimulated mitophagy and cartilage degradation by upregulating cartilage-degrading enzymes and chondrocyte death. We identified microRNA (miR)-126-5p as an upstream regulator for PGC1\u03b1 and confirmed the direct binding between miR-126-5p and 3\u2032 untranslated region (UTR) of PGC1\u03b1. An in vivo OA mouse model induced by the destabilization of medial meniscus (DMM) surgery, and the delivery of antago-miR-126 via intra-articular injection significantly decreased cartilage degradation. In sum, the loss of PGC1\u03b1 in chondrocytes due to upregulation of miR-126-5p during OA pathogenesis resulted in the activation of PRKN-independent mitophagy through the upregulation of BNIP3 and stimulated cartilage degradation and apoptotic death of chondrocytes. Therefore, the regulation of PGC1\u03b1:BNIP3 mitophagy axis could be of therapeutic benefit to cartilage-degrading diseases.<\/jats:p>","DOI":"10.3390\/cells10071839","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T11:26:10Z","timestamp":1626780370000},"page":"1839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["BNIP3-Dependent Mitophagy via PGC1\u03b1 Promotes Cartilage Degradation"],"prefix":"10.3390","volume":"10","author":[{"given":"Deokha","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan 54538, Jeonbuk, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsoo","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan 54538, Jeonbuk, Korea"},{"name":"Integrated Omics Institute, Wonkwang University, Iksan 54538, Jeonbuk, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6874-3017","authenticated-orcid":false,"given":"Eun-Jung","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan 54538, Jeonbuk, Korea"},{"name":"Integrated Omics Institute, Wonkwang University, Iksan 54538, Jeonbuk, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.berh.2005.09.007","article-title":"Osteoarthritis: Epidemiology","volume":"20","author":"Arden","year":"2006","journal-title":"Best Pract. 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