The metal-organic framework MIL-100(Fe) and ferric citrate as potential counteracting biomaterials against osteoarthritis-induced articular inflammation and fibrosis

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Osteoarthritis (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. ● Osteoarthritis features inflammation, structural destruction, calcification, and fibrosis of the articular joints. ● Ferric citrate attenuates inflammatory cytokine IL6-induced synovial epithelial cell injury and promotes cell proliferation. ● ML100 alleviated IL6- and TGFβ1-induced fibrosis protein expressions and reduced extracellular matrix protein production. ● A combination of ferric citrate with ML100 may enhance therapeutic efficacy against osteoarthritis.