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

  • In-A Cho
  • Tae-Hyeon Kim
  • HyangI Lim
  • Jong-Hyun Park
  • Kyeong-Rok Kang
  • Sook-Young Lee
  • Chun Sung Kim
  • Do Kyung Kim
  • Heung-Joong Kim
  • Sun-Kyoung Yu
  • Su-Gwan Kim
  • Jae-Sung KimEmail author


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 E2 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.


osteoarthritis articular cartilage chondrocyte inflammation formononetin 



This study was supported by research fund from Chosun University, 2017.

Author’s Contributions

I.A.C, T.H.K., K.R.K, H.L., J.H.P., S.Y.L., and J.S.K. contributed to the experimental design and collected the data. C.S.K., D.K.K., H.K.K., S.K.Y., S.G.K., and J.S.K. contributed to the data analysis and interpretation. I.A.C., K.R.K., and J.S.K. did the writing article.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • In-A Cho
    • 1
  • Tae-Hyeon Kim
    • 1
  • HyangI Lim
    • 1
  • Jong-Hyun Park
    • 1
  • Kyeong-Rok Kang
    • 1
  • Sook-Young Lee
    • 1
    • 2
  • Chun Sung Kim
    • 1
    • 2
  • Do Kyung Kim
    • 1
  • Heung-Joong Kim
    • 1
  • Sun-Kyoung Yu
    • 1
  • Su-Gwan Kim
    • 1
  • Jae-Sung Kim
    • 1
    Email author
  1. 1.Oral Biology Research Institute, School of DentistryChosun UniversityGwangjuRepublic of Korea
  2. 2.Marine Bio Research CenterChosun UniversityWando-gunRepublic of Korea

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