Tsai, Pei-ShiuePei-ShiueTsaiWu, Kevin C.-W.Kevin C.-W.WuWu, Ching-HoChing-HoWu2026-01-202026-01-202025-1007533322https://www.scopus.com/record/display.uri?eid=2-s2.0-105014290152&origin=resultslisthttps://scholars.lib.ntu.edu.tw/handle/123456789/735521Osteoarthritis (OA) is a degenerative and deteriorating disease. The accompanying pain, stiffness, inflammation of the synovial joint, and the loss of articular function compromise the mobility, stability, and routine of patients’ lives. As inflammation-associated structural destruction, calcification, and fibrosis are common features observed in OA patients, nonsteroidal anti-inflammatory drugs have been first-line analgesics for the management of OA in both humans and animals. In this study, we mimicked in vitro OA-induced articular inflammation and fibrosis and evaluated the phenotypical alterations of synovial-like lining cells and fibroblasts under the treatment of ferric citrate, an iron(III) citrate compound, and metal-organic frameworks (MIL-100(Fe)), a multiporous drug carrier material, to explore the therapeutic potential of these compounds in canine OA patients. Our data demonstrated that ferric citrate reduced inflammatory cytokine interleukin 6-induced cell injury and promoted their cell proliferation; on the other hand, MIL-100(Fe) effectively mitigated IL6- and TGFβ1-induced fibrosis marker proteins, such as transforming growth factor beta 1, alpha smooth muscle actin, collagen type I, small mother against decapentaplegic 2/3 expressions, but did not enhance the regeneration or proliferation of the synovial-like lining cells, indicating the distinct therapeutic potential of ferric citrate and MIL-100(Fe). Although neither ferric citrate nor ML100(Fe) restored the mitochondrial function, the combination of ferric citrate with ML100(Fe) may enhance the therapeutic efficacy of OA-induced articular inflammation at early stages to prevent further progression toward articular fibrosis and provide better therapeutic outcomes for canine OA patients.trueCanineFerric citrateMetal-organic frameworksOsteoarthritisSynovial jointjournal article10.1016/j.biopha.2025.1185192-s2.0-105014290152