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Inhibition of matrix metalloproteinase-13 expression in IL-1β-treated articular chondrocytes by a steroidal saponin, spicatoside A, and its cellular mechanisms of action

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Abstract

Matrix metalloproteinase-13 (MMP-13) plays a critical role in degrading major collagens in human cartilage under some pathological conditions such as osteoarthritis. To establish the therapeutic potential against cartilage degradation, the effects of 12 naturally-occurring triterpenoids and steroids on MMP-13 induction were examined in the human chondrocyte cell line, SW1353. They included coreanoside F1, suavissimoside R1, spicatoside A, 25(S)-ruscogenin, methyl protogracillin, hederagenin, loniceroside A, loniceroside B, loniceroside C, smilaxin A, smilaxin C, and ursolic acid. Among these, only spicatoside A and 25(S)-ruscogenin were found to inhibit MMP-13 expression in IL-1β-treated SW1353 cells at a pharmacologically-relevant concentration of 10 μM. These effects were also supported by the finding that spicatoside A (20 μM) reduced glycosaminoglycan release from IL-1α-treated rabbit joint cartilage culture to some degree. When the cellular mechanisms of action of spicatoside A in MMP-13 inhibition were investigated, the blocking point was not found among the MMP-13 signaling molecules examined such as mitogen-activated protein kinases, activator protein-1, and nuclear transcription factor-κB. Instead, spicatoside A was found to reduce MMP-13 mRNA stability. All of these findings suggest that spicatoside A and 25(S)-ruscogenin have a therapeutic potential for protecting against cartilage breakdown in arthritic disorders.

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Acknowledgments

This study was supported by BK21-plus Project from the Korean Ministry of Education. The bioassay facility of New Drug Res. Institute (KNU) was used and greatly acknowledged.

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The authors indicated no potential conflicts of interest.

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Authors and Affiliations

  1. College of Pharmacy, Kangwon National University, Chuncheon, 200-701, Korea

    Hyun Lim, Dong Suk Min, Yuna Kang, Hyeong Won Kim & Hyun Pyo Kim

  2. Department of Food and Nutrition, Andong National University, Andong, 760-749, Korea

    Kun Ho Son

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  1. Hyun Lim
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  2. Dong Suk Min
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  3. Yuna Kang
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  4. Hyeong Won Kim
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  5. Kun Ho Son
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Correspondence to Hyun Pyo Kim.

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Lim, H., Min, D.S., Kang, Y. et al. Inhibition of matrix metalloproteinase-13 expression in IL-1β-treated articular chondrocytes by a steroidal saponin, spicatoside A, and its cellular mechanisms of action. Arch. Pharm. Res. 38, 1108–1116 (2015). https://doi.org/10.1007/s12272-015-0581-z

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  • DOI: https://doi.org/10.1007/s12272-015-0581-z

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