{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:43:57Z","timestamp":1790156637527,"version":"4.0.1"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974350"],"award-info":[{"award-number":["81974350"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2020CFA019"],"award-info":[{"award-number":["2020CFA019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["YCJJ202201023"],"award-info":[{"award-number":["YCJJ202201023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Hubei","award":["81974350"],"award-info":[{"award-number":["81974350"]}]},{"name":"Natural Science Foundation of Hubei","award":["2020CFA019"],"award-info":[{"award-number":["2020CFA019"]}]},{"name":"Natural Science Foundation of Hubei","award":["YCJJ202201023"],"award-info":[{"award-number":["YCJJ202201023"]}]},{"name":"Research Funds for the Central Universities","award":["81974350"],"award-info":[{"award-number":["81974350"]}]},{"name":"Research Funds for the Central Universities","award":["2020CFA019"],"award-info":[{"award-number":["2020CFA019"]}]},{"name":"Research Funds for the Central Universities","award":["YCJJ202201023"],"award-info":[{"award-number":["YCJJ202201023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA), the most common chronic inflammatory joint disease, is characterized by progressive cartilage degeneration, subchondral bone sclerosis, synovitis, and osteophyte formation. Metformin, a hypoglycemic agent used in the treatment of type 2 diabetes, has been evidenced to have anti-inflammatory properties to treat OA. It hampers the M1 polarization of synovial sublining macrophages, which promotes synovitis and exacerbates OA, thus lessening cartilage loss. In this study, metformin prevented the pro-inflammatory cytokines secreted by M1 macrophages, suppressed the inflammatory response of chondrocytes cultured with conditional medium (CM) from M1 macrophages, and mitigated the migration of M1 macrophages induced by interleukin-1\u00df (IL-1\u00df)-treated chondrocytes in vitro. In the meantime, metformin reduced the invasion of M1 macrophages in synovial regions brought about by the destabilization of medial meniscus (DMM) surgery in mice, and alleviated cartilage degeneration. Mechanistically, metformin regulated PI3K\/AKT and downstream pathways in M1 macrophages. Overall, we demonstrated the therapeutic potential of metformin targeting synovial M1 macrophages in OA.<\/jats:p>","DOI":"10.3390\/ijms24065355","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T05:36:21Z","timestamp":1678685781000},"page":"5355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Metformin Attenuates the Inflammatory Response via the Regulation of Synovial M1 Macrophage in Osteoarthritis"],"prefix":"10.3390","volume":"24","author":[{"given":"Meng","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanli","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6211-6047","authenticated-orcid":false,"given":"Kang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxu","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renpeng","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6472-1833","authenticated-orcid":false,"given":"Jun","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16072","DOI":"10.1038\/nrdp.2016.72","article-title":"Osteoarthritis","volume":"2","author":"Barr","year":"2016","journal-title":"Nat. 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