{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:21:17Z","timestamp":1791404477476,"version":"4.3.3"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,20]],"date-time":"2022-02-20T00:00:00Z","timestamp":1645315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the research fund of Rheumatology Research Foundation","award":["RRF-2017-05"],"award-info":[{"award-number":["RRF-2017-05"]}]},{"name":"Chungnam National University Hospital Research Fund","award":["2018"],"award-info":[{"award-number":["2018"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1G1A1005712"],"award-info":[{"award-number":["NRF-2021R1G1A1005712"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to examine the role of CD70, which is highly expressed on fibroblast-like synoviocytes (FLS), in rheumatoid arthritis (RA) patients. FLS isolated from RA (n = 14) and osteoarthritis (OA, n = 4) patients were stimulated with recombinant interleukin-17 (IL-17; 5 ng\/mL) and tumor necrosis factor alpha (TNF-\u03b1; 5 ng\/mL) for 24 h. Expression of CD70, CD27\/soluble CD27 (sCD27), and hypoxia-inducible factor-2 alpha (HIF-2\u03b1) was analyzed by RT-qPCR, flow cytometry, and ELISA assays, respectively. Reactive oxygen species (ROS) expression and cell migration were also examined. The HIF-2\u03b1 inhibitor PT-2385 and CD70 inhibitor BU69 were used to specifically suppress these pathways. Stimulation with IL-17 and TNF-\u03b1 significantly induced CD70 expression in RA FLS. Although the synovial fluids from patients with RA contained high levels of sCD27, surface expression of CD27, a ligand of CD70, was rarely detected in RA FLS. Cytokine-induced CD70 expression was significantly decreased following antioxidant treatment. Following HIF-2\u03b1 inhibition, RA FLS had decreased expression of CD70 and ROS levels. Migration of RA FLS was also inhibited by inhibition of CD70 or HIF-2\u03b1. The surface expression of CD70 is regulated by HIF-2\u03b1 and ROS levels and is a key contributor to cytokine-enhanced migration in RA FLS.<\/jats:p>","DOI":"10.3390\/ijms23042342","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T09:19:39Z","timestamp":1645435179000},"page":"2342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Hypoxia-Inducible Factor-2 Alpha Regulates the Migration of Fibroblast-like Synoviocytes via Oxidative Stress-Induced CD70 Expression in Patients with Rheumatoid Arthritis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4620-8803","authenticated-orcid":false,"given":"Su-Jin","family":"Yoo","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwaro, Daejeon 35015, Korea"},{"name":"Research Institute for Medical Sciences, Chungnam National University School of Medicine, 266 Munhwaro, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha-Reum","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwaro, Daejeon 35015, Korea"},{"name":"Research Institute for Medical Sciences, Chungnam National University School of Medicine, 266 Munhwaro, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwaro, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5380-5895","authenticated-orcid":false,"given":"In Seol","family":"Yoo","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Chungnam National University Sejong Hospital, 20 Bodeum-7-ro, Sejong 30099, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Keol","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Chungnam National University Sejong Hospital, 20 Bodeum-7-ro, Sejong 30099, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0076-0822","authenticated-orcid":false,"given":"Seong Wook","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, 282 Munhwaro, Daejeon 35015, Korea"},{"name":"Research Institute for Medical Sciences, Chungnam National University School of Medicine, 266 Munhwaro, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nature01661","article-title":"Evolving concepts of rheumatoid arthritis","volume":"423","author":"Firestein","year":"2003","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/S0140-6736(12)62192-8","article-title":"Rheumatoid arthritis: Still a chronic disease","volume":"381","author":"Miossec","year":"2013","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/ar2107","article-title":"Cells of the synovium in rheumatoid arthritis. 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