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Formononetin Antagonizes the Interleukin-1β-Induced Catabolic Effects Through Suppressing Inflammation in Primary Rat Chondrocytes

In the present study, we demonstrated the anti-catabolic effects of formononetin, a phytoestrogen derived from herbal plants, against interleukin-1β (IL-1β)-induced severe catabolic effects in primary rat chondrocytes and articular cartilage. Formononetin did not affect the viability of primary rat...

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Published in:Inflammation 2019-08, Vol.42 (4), p.1426-1440
Main Authors: Cho, In-A, Kim, Tae-Hyeon, Lim, HyangI, Park, Jong-Hyun, Kang, Kyeong-Rok, Lee, Sook-Young, Kim, Chun Sung, Kim, Do Kyung, Kim, Heung-Joong, Yu, Sun-Kyoung, Kim, Su-Gwan, Kim, Jae-Sung
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Language:English
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Summary:In the present study, we demonstrated the anti-catabolic effects of formononetin, a phytoestrogen derived from herbal plants, against interleukin-1β (IL-1β)-induced severe catabolic effects in primary rat chondrocytes and articular cartilage. Formononetin did not affect the viability of primary rat chondrocytes in both short- (24 h) and long-term (21 days) treatment periods. Furthermore, formononetin effectively antagonized the IL-1β-induced catabolic effects including the decrease in proteoglycan content, suppression of pericellular matrix formation, and loss of proteoglycan through the decreased expression of cartilage-degrading enzymes like matrix metalloproteinase (MMP)-13, MMP-1, and MMP-3 in primary rat chondrocytes. Moreover, catabolic oxidative stress mediators like nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, and prostaglandin E 2 were significantly downregulated by formononetin in primary rat chondrocytes treated with IL-1β. Sequentially, the upregulation of pro-inflammatory cytokines (like IL-1α, IL-1β, IL-6, and tumor necrosis factor α), chemokines (like fractalkine, monocyte chemoattractant protein-1, and macrophage inflammatory protein-3α), and vascular endothelial growth factor were significantly downregulated by formononetin in primary rat chondrocytes treated with IL-1β. These data suggest that formononetin may suppress IL-1β-induced severe catabolic effects and osteoarthritic condition. Furthermore, formononetin may be a promising candidate for the treatment and prevention of osteoarthritis.
ISSN:0360-3997
1573-2576
DOI:10.1007/s10753-019-01005-1