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In this study, we observed impaired mitophagy and glucose metabolism disorders in OA chondrocytes, which exacerbated cartilage degeneration. And we unveil\n                    <jats:italic>Chlorella<\/jats:italic>\n                    , a natural microorganism that appeared more than two billion years ago, as an efficient regulator of both mitophagy and glucose metabolism in OA chondrocytes.\n                    <jats:italic>Chlorella<\/jats:italic>\n                    activates mitophagy and rescues mitochondrial function. More importantly,\n                    <jats:italic>Chlorella<\/jats:italic>\n                    inhibits glycolysis and reprograms glucose metabolism in chondrocytes, leading to the remodelling of chondrocyte homeostasis and alleviation of cartilage degeneration both in vitro and in vivo. As a proof of concept, we constructed a photothermal\n                    <jats:italic>Chlorella<\/jats:italic>\n                    biohybrid (Ch@P) that induced articular thermal stimulation under near\u2010infrared irradiation and significantly strengthened the protection against cartilage degeneration in DMM mouse models of OA. Ch@P activates the AMPK\u2010Sirt1 signalling pathway to restore mitochondrial homeostasis and energy metabolism in chondrocytes. Furthermore, HSP70 is also activated to regulate chondrocyte homeostasis due to articular thermal stimulation. Our study unveils the activity of natural\n                    <jats:italic>Chlorella<\/jats:italic>\n                    in chondrocyte homeostasis by activating mitophagy and reprogramming glucose metabolism and identifies an artificial Chlorella biohybrid as a promising therapeutic option for OA treatment.\n                  <\/jats:p>","DOI":"10.1002\/exp.20250125","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T03:00:29Z","timestamp":1783738829000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Artificial Chlorella Biohybrids for Alleviation of Cartilage Degeneration in Osteoarthritis"],"prefix":"10.1002","volume":"6","author":[{"given":"Yongyun","family":"Chang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants Department of Orthopedics Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyu","family":"Kong","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants Department of Orthopedics Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Jin","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants Department of Orthopedics Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopedic Implants Department of Orthopedics Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Engineering Research Center of Innovative Orthopaedic Instruments and Personalized Medicine Clinical and Translational Research Center for 3D Printing Technology  Shanghai China"},{"name":"Department of Rehabilitation Medicine Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangzi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Spine Center Changzheng Hospital Navy Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Inorganic Coating Materials Shanghai Institute of Ceramics Chinese Academy of Sciences  Shanghai P. 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