{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:31:45Z","timestamp":1793327505403,"version":"4.5.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:p>\n                    Inflammation and loss of articular cartilage are considered the major cause of temporomandibular joint osteoarthritis (TMJOA), a painful condition of the temporomandibular joint (TMJ). To determine the cause of TMJ osteoarthritis in these patients, synovial fluid of TMJOA patients was compared prior to and after hyaluronic lavage, revealing substantially elevated levels of interleukin (IL) 1\u03b2, reactive oxidative stress (ROS), and an overload of Fe\n                    <jats:sup>3+<\/jats:sup>\n                    and Fe\n                    <jats:sup>2+<\/jats:sup>\n                    prior to lavage, indicative of ferroptosis as a mode of chondrocyte cell death. To ask whether prolonged inflammatory conditions resulted in ferroptosis-like transformation in vitro, we subjected TMJ chondrocytes to IL-1\u03b2 treatment, resulting in a shift in messenger RNA sequencing gene ontologies related to iron homeostasis and oxidative stress\u2013related cell death. Exposure to rat unilateral anterior crossbite conditions resulted in reduced COL2A1 expression, fewer chondrocytes, glutathione peroxidase 4 (GPX4) downregulation, and 4-hydroxynonenal (4-HNE) upregulation, an effect that was reversed after intra-articular injections of the ferroptosis inhibitor ferrostatin 1 (Fer-1). Our study demonstrated that ferroptosis conditions affected mitochondrial structure and function, while the inhibitor Fer-1 restored mitochondrial structure and the inhibition of hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) or the transferrin receptor 1 (TFRC) rescued IL-1\u03b2\u2013induced loss of mitochondrial membrane potential. Inhibition of HIF-1\u03b1 downregulated IL-1\u03b2\u2013induced TFRC expression, while inhibition of TFRC did not downregulate IL-1\u03b2\u2013induced HIF-1\u03b1 expression in chondrocytes. Moreover, inhibition of HIF-1\u03b1 or TFRC downregulated the IL-1\u03b2\u2013induced MMP13 expression in chondrocytes, while inhibition of HIF-1\u03b1 or TFRC rescued IL-1\u03b2\u2013inhibited COL2A1 expression in chondrocytes. Furthermore, upregulation of TFRC promoted Fe\n                    <jats:sup>2+<\/jats:sup>\n                    entry into chondrocytes, inducing the Fenton reaction and lipid peroxidation, which in turn caused ferroptosis, a disruption in chondrocyte functions, and an exacerbation of condylar cartilage degeneration. Together, these findings illustrate the far-reaching effects of chondrocyte ferroptosis in TMJOA as a mechanism causing chondrocyte death through iron overload, oxidative stress, and articular cartilage degeneration and a potential major cause of TMJOA.\n                  <\/jats:p>","DOI":"10.1177\/00220345241242389","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T04:59:45Z","timestamp":1716181185000},"page":"712-722","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":96,"title":["Inflammation Triggers Chondrocyte Ferroptosis in TMJOA via HIF-1\u03b1\/TFRC"],"prefix":"10.1177","volume":"103","author":[{"given":"B.Y.","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.L.","family":"Pathak","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.Y.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.Q.","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.J.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, China"},{"name":"Vascular Biology Research Institute, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.F.","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Medicine and Dentistry University of Rochester, Rochester, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-9677","authenticated-orcid":false,"given":"T.G.H.","family":"Diekwisch","sequence":"additional","affiliation":[{"name":"School of Medicine and Dentistry University of Rochester, Rochester, NY, 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