{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T07:25:34Z","timestamp":1767597934442,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korean government","award":["NRF-2022R1A2C1003890"],"award-info":[{"award-number":["NRF-2022R1A2C1003890"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dexmedetomidine (Dex) has analgesic and sedative properties and anti-inflammatory functions. Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been fully studied. Inflamed and migrated fibroblast-like synoviocytes (FLSs) are involved in RA severity. Thus, we aimed to determine the effects of Dex on RA-FLSs treated with inflammatory cytokines and a growth factor as multiple stimulating inputs. TNF-\u03b1, IL-6, and EGF as multiple stimulating inputs increased the cAMP concentration of RA-FLSs, while Dex treatment reduced cAMP concentration. Dex reduced electroneutral sodium-bicarbonate cotransporter 1 (NBCn1) expression, NBC activity, and subsequent RA-FLS migration. The mRNA expression levels of RA-related factors, such as inflammatory cytokines and osteoclastogenesis factors, were enhanced by multiple-input treatment. Notably, Dex effectively reduced these expression levels in RA-FLSs. These results indicate that multiple inflammatory or stimulating inputs enhance RA-FLS migration, and treatment with Dex relieves activated RA-FLSs, suggesting that Dex is a potential therapeutic drug for RA.<\/jats:p>","DOI":"10.3390\/ijms241310756","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:41:45Z","timestamp":1687999305000},"page":"10756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the \u03b12-Adrenergic Receptor Agonist Dexmedetomidine"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1990-2533","authenticated-orcid":false,"given":"Dongun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Health Sciences and Technology, Lee Gil Ya Cancer and Diabetes Institute, GAIHST, Gachon University, 155 Getbeolro, Yeonsu-gu, Incheon 21999, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3623-2201","authenticated-orcid":false,"given":"Jeong Hee","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology, Lee Gil Ya Cancer and Diabetes Institute, GAIHST, Gachon University, 155 Getbeolro, Yeonsu-gu, Incheon 21999, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1302\/2046-3758.104.BJR-2020-0331.R1","article-title":"Signalling and putative therapeutic molecules on the regulation of synoviocyte signalling in rheumatoid arthritis","volume":"10","author":"Ji","year":"2021","journal-title":"Bone Jt. 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