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Fibroblast growth factor 8 (FGF8) is a multipotent protein ligand which is upregulated in OA cartilage. However, the molecular mechanisms by which FGF8 regulates mitochondria in chondrocytes are not yet fully understood. Here, we treated chondrocytes with FGF8 and detected the effects of FGF8 on mitochondrial morphology in the cytoplasm using transmission electron and confocal laser scanning microscopy. ATP levels were measured to determine the cellular energy status. Western blotting and immunofluorescence staining experiments were employed to detect the fusion\u2010fission proteins mitofusin 1 (MFN1), mitofusin 2 (MFN2), optic atrophy 1 (OPA1), dynamin\u2010related protein 1 (DRP1), mitochondrial fission 1 protein (FIS1), and related signaling pathways. The FGF receptor (FGFR) inhibitor, AZD4547, and the ERK inhibitor, U0126, were used to verify the specific effects of the FGFR and ERK pathways. We found that FGF8 regulated mitochondrial morphology and dynamics in chondrocytes by inducing mitochondrial elongation. While it upregulated fusion proteins MFN1, MFN2, and OPA1, FGF8 downregulated fission proteins DRP1 and FIS1. ERK and AMPK pathways were activated in chondrocytes after FGF8 treatment. In contrast, both AZD4547 and U0126 inhibitors abolished mitochondrial elongation as well as the alteration of fusion\u2010fission proteins induced by FGF8, and U0126 also inhibited the FGF8\u2010triggered activation of AMPK. This study is the first to reveal that FGF8 remodels mitochondria through ERK\/AMPK signaling in chondrocytes, offering novel insights into the potential role of FGF8 in OA.<\/jats:p>","DOI":"10.1096\/fj.202500186r","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T08:44:35Z","timestamp":1743497075000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Fibroblast growth factor 8 (\n                    <scp>FGF8<\/scp>\n                    ) induces mitochondrial remodeling in chondrocytes via\n                    <scp>ERK<\/scp>\n                    \/\n                    <scp>AMPK<\/scp>\n                    signaling pathway"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7543-5879","authenticated-orcid":false,"given":"Hongcan","family":"Huang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National 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