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Inflammation

, Volume 40, Issue 1, pp 79–91 | Cite as

Coumestrol Counteracts Interleukin-1β-Induced Catabolic Effects by Suppressing Inflammation in Primary Rat Chondrocytes

  • Jae-Seek You
  • In-A Cho
  • Kyeong-Rok Kang
  • Ji-Su Oh
  • Sang-Joun Yu
  • Gyeong-Je Lee
  • Yo-Seob Seo
  • Su-Gwan Kim
  • Chun Sung Kim
  • Do Kyung Kim
  • Hee-Jeong Im
  • Jae-Sung KimEmail author
ORIGINAL ARTICLE

Abstract

In the present study, we investigated the anti-catabolic effects of coumestrol, a phytoestrogen derived from herbal plants, against interleukin-1β-induced cartilage degeneration in primary rat chondrocytes and articular cartilage. Coumestrol did not affect the viability of human normal oral keratinocytes and primary rat chondrocytes treated for 24 h and 21 days, respectively. Although coumestrol did not significantly increase the proteoglycan contents in long-term culture, it abolished the interleukin-1β-induced loss of proteoglycans in primary rat chondrocytes and knee articular cartilage. Furthermore, coumestrol suppressed the expression of matrix-degrading enzymes such as matrix metalloproteinase-13, −3, and −1 in primary rat chondrocytes stimulated with interleukin-1β. Moreover, the expression of catabolic factors such as nitric oxide synthase, cyclooxygenase-2, prostaglandin E2, and inflammatory cytokines in interleukin-1β-stimulated primary rat chondrocytes was suppressed by coumestrol. In summary, these results indicate that coumestrol counteracts the catabolic effects induced by interleukin-1β through the suppression of inflammation. Therefore, based on its biological activity and safety profile, coumestrol could be used as a potential anti-catabolic biomaterial for osteoarthritis.

KEY WORDS

osteoarthritis inflammation chondrocyte coumestrol anti-catabolic effects 

Notes

Acknowledgments

This study was supported by research fund from Chosun University Dental Hospital, 2015.

Authors’ Contributions

J.S.Y., I.A.C., K,R.K., J.S.O., and J.S.K. contributed to the experimental design and collected the data. S.J.Y., G.J.L., Y.S.S., S.G.K., C.S.K., and J.S.K. contributed to the data analysis. J.S.Y., H.J.I., D.K.K., and J.S.K. did the writing and revisions of articles.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Kean, W.F., R. Kean, and W.W. Buchanan. 2004. Osteoarthritis: symptoms, signs and source of pain. Inflammopharmacology 12: 3–31.CrossRefPubMedGoogle Scholar
  2. 2.
    Akkiraju, H., and A. Nohe. 2015. Role of chondrocytes in cartilage formation, progression of osteoarthritis and cartilage regeneration. Journal of Developmental Biology 3: 177–192.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Crepaldi, G., and L. Punzi. 2003. Aging and osteoarthritis. Aging Clinical and Experimental Research 15: 355–358.CrossRefPubMedGoogle Scholar
  4. 4.
    Greene, M.A., and R.F. Loeser. 2015. Aging-related inflammation in osteoarthritis. Osteoarthritis and Cartilage 23: 1966–1971.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Loeser, R.F. 2009. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthritis and Cartilage 17: 971–979.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Le Maitre, C.L., A. Pockert, D.J. Buttle, A.J. Freemont, and J.A. Hoyland. 2007. Matrix synthesis and degradation in human intervertebral disc degeneration. Biochemical Society Transactions 35: 652–655.CrossRefPubMedGoogle Scholar
  7. 7.
    Kim, J.S., M.B. Ellman, H.S. An, A.J. van Wijnen, J.A. Borgia, and H.J. Im. 2010. Insulin-like growth factor 1 synergizes with bone morphogenetic protein 7-mediated anabolism in bovine intervertebral disc cells. Arthritis and Rheumatism 62: 3706–37015.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Martín-Millán, M., and S. Castañeda. 2013. Estrogens, osteoarthritis and inflammation. Joint, Bone, Spine 80: 368–373.CrossRefPubMedGoogle Scholar
  9. 9.
    Lee, G.J., I.A. Cho, K.R. Kang, K. Kim do, H.M. Sohn, J.W. You, J.S. Oh, Y.S. Seo, S.J. Yu, J.S. You, C.S. Kim, S.G. Kim, H.J. Im, and J.S. Kim. 2015. Biological effects of the herbal plant-derived phytoestrogen bavachin in primary rat chondrocytes. Biological & Pharmaceutical Bulletin 38: 1199–1207.CrossRefGoogle Scholar
  10. 10.
    Bickoff, E.M., A.N. Booth, R.L. Lyman, A.L. Livingston, C.R. Thompson, and F. Deeds. 1957. Coumestrol, a new estrogen isolated from forage crops. Science 126: 969–970.CrossRefPubMedGoogle Scholar
  11. 11.
    Bickoff, E.M., A.L. Livingston, and A.N. Booth. 1960. Estrogenic activity of coumestrol and related compounds. Archives of Biochemistry and Biophysics 88: 262–266.CrossRefPubMedGoogle Scholar
  12. 12.
    Jantaratnotai, N., P. Utaisincharoen, P. Sanvarinda, A. Thampithak, and Y. Sanvarinda. 2013. Phytoestrogens mediated anti-inflammatory effect through suppression of IRF-1 and pSTAT1 expressions in lipopolysaccharide-activated microglia. International Immunopharmacology 17: 483–488.CrossRefPubMedGoogle Scholar
  13. 13.
    Jin, S.E., Y.K. Son, B.S. Min, H.A. Jung, and J.S. Choi. 2012. Anti-inflammatory and antioxidant activities of constituents isolated from Pueraria lobata roots. Archives of Pharmacal Research 35: 823–837.CrossRefPubMedGoogle Scholar
  14. 14.
    Oh, J.S., I.A. Cho, K.R. Kang, J.S. You, S.J. Yu, G.J. Lee, Y.S. Seo, C.S. Kim, K. Kim do, S.G. Kim, Y.W. Seo, H.J. Im, and J.S. Kim. 2016. Biochanin-A antagonizes the interleukin-1beta-induced catabolic inflammation through the modulation of NFkB cellular signaling in primary rat chondrocytes. Biochemical and Biophysical Research Communications 477: 723–730.CrossRefPubMedGoogle Scholar
  15. 15.
    Kim, J.S., M.B. Ellman, H.S. An, D. Yan, A.J. van Wijnen, G. Murphy, D.W. Hoskin, and H.J. Im. 2012. Lactoferricin mediates anabolic and anti-catabolic effects in the intervertebral disc. Journal of Cellular Physiology 227: 1512–1520.CrossRefPubMedGoogle Scholar
  16. 16.
    Park, M.R., S.G. Kim, I.A. Cho, D. Oh, K.R. Kang, S.Y. Lee, S.M. Moon, S.S. Cho, G. Yoon, C.S. Kim, J.S. Oh, J.S. You, D.K. Kim, Y.S. Seo, H.J. Im, and J.S. Kim. 2015. Licochalcone-A induces intrinsic and extrinsic apoptosis via ERK1/2 and p38 phosphorylation-mediated TRAIL expression in head and neck squamous carcinoma FaDu cells. Food and Chemical Toxicology 77: 34–43.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Kim, J.S., M.B. Ellman, D. Yan, H.S. An, R. Kc, X. Li, D. Chen, G. Xiao, G. Cs-Szabo, D.W. Hoskin, D.D. Buechter, A.J. Van Wijnen, and H.J. Im. 2013. Lactoferricin mediates anti-inflammatory and anti-catabolic effects via inhibition of IL-1 and LPS activity in the intervertebral disc. Journal of Cellular Physiology 228: 1884–1896.CrossRefPubMedGoogle Scholar
  18. 18.
    Heidari, B. 2011. Knee osteoarthritis prevalence, risk factors, pathogenesis and features: Part I. Caspian Journal of Internal Medicine 2: 205–212.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Huang, B.J., J.C. Hu, and K.A. Athanasiou. 2016. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage. Biomaterials 98: 1–22.CrossRefPubMedGoogle Scholar
  20. 20.
    Lee, A.S., M.B. Ellman, D. Yan, J.S. Kroin, B.J. Cole, A.J. van Wijnen, and H.J. Im. 2013. A current review of molecular mechanisms regarding osteoarthritis and pain. Gene 527: 440–447.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Oshima, A., W. Mine, M. Nakada, and E. Yanase. 2016. Analysis of isoflavones and coumestrol in soybean sprouts. Bioscience Biotechnology and Biochemistry 13: 1–3.Google Scholar
  22. 22.
    Knuckles, B.E., D. deFremery, and G.O. Kohler. 1976. Coumestrol content of fractions obtained during wet processing of alfalfa. Journal of Agricultural and Food Chemistry 24: 1177–1180.CrossRefPubMedGoogle Scholar
  23. 23.
    Sokolove, J., and C.M. Lepus. 2013. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Therapeutic Advances in Musculoskeletal Disease 5: 77–94.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Hedbom, E., and H.J. Hauselmann. 2002. Molecular aspects of pathogenesis in osteoarthritis: the role of inflammation. Cellular and Molecular Life Sciences 59: 45–53.CrossRefPubMedGoogle Scholar
  25. 25.
    Archer, C.W., and P. Francis-West. 2003. The chondrocyte. The International Journal of Biochemistry & Cell Biology 35: 401–404.CrossRefGoogle Scholar
  26. 26.
    Reed, K.N., G. Wilson, A. Pearsall, and V.I. Grishko. 2014. The role of mitochondrial reactive oxygen species in cartilage matrix destruction. Molecular and Cellular Biochemistry 397: 195–201.CrossRefPubMedGoogle Scholar
  27. 27.
    Ruiz-Romero, C., V. Calamia, J. Mateos, V. Carreira, M. Martinez-Gomariz, M. Fernandez, and F.J. Blanco. 2009. Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance. Molecular & Cellular Proteomics 8: 172–189.CrossRefGoogle Scholar
  28. 28.
    Henrotin, Y.E., P. Bruckner, and J.P. Pujol. 2003. The role of reactive oxygen species in homeostasis and degradation of cartilage. Osteoarthritis and Cartilage 11: 747–755.CrossRefPubMedGoogle Scholar
  29. 29.
    Konttinen, Y.T., T. Sillat, G. Barreto, M. Ainola, and D.C.E. Nordstrom. 2012. Osteoarthritis as an autoinflammatory disease caused by chondrocyte-mediated inflammatory responses. Arthritis and Rheumatism 64: 613–616.CrossRefPubMedGoogle Scholar
  30. 30.
    Berenbaum, F. 2013. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis and Cartilage 21: 16–21.CrossRefPubMedGoogle Scholar
  31. 31.
    Yuan, P.W., D.Y. Liu, X.D. Chu, Y.Q. Hao, C. Zhu, and Q.A. Qu. 2010. Effects of preventive administration of juanbi capsules on TNF-alpha, IL-1 and IL-6 contents of joint fluid in the rabbit with knee osteoarthritis. Journal of Traditional Chinese Medicine 30: 254–258.CrossRefPubMedGoogle Scholar
  32. 32.
    Sandell, L.J., X. Xing, C. Franz, S. Davies, L.W. Chang, and D. Patra. 2008. Exuberant expression of chemokine genes by adult human articular chondrocytes in response to IL-1beta. Osteoarthritis and Cartilage 16: 1560–1571.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Ruth, J.H., S. Shahrara, C.C. Park, J.C. Morel, P. Kumar, S. Qin, and A.E. Koch. 2003. Role of macrophage inflammatory protein-3alpha and its ligand CCR6 in rheumatoid arthritis. Laboratory Investigation 83: 579–588.CrossRefPubMedGoogle Scholar
  34. 34.
    Yoshida, K., O. Korchynskyi, P.P. Tak, T. Isozaki, J.H. Ruth, P.L. Campbell, D.L. Baeten, D.M. Gerlag, M.A. Amin, and A.E. Koch. 2014. Citrullination of epithelial neutrophil-activating peptide 78/CXCL5 results in conversion from a non-monocyte-recruiting chemokine to a monocyte-recruiting chemokine. Arthritis and Rheumatology 66: 2716–2727.CrossRefPubMedGoogle Scholar
  35. 35.
    Huo, L.W., Y.L. Ye, G.W. Wang, and Y.G. Ye. 2015. Fractalkine (CX3CL1): a biomarker reflecting symptomatic severity in patients with knee osteoarthritis. Journal of Investigative Medicine 63: 626–631.CrossRefPubMedGoogle Scholar
  36. 36.
    Akhtar, N., and T.M. Haqqi. 2011. Epigallocatechin-3-gallate suppresses the global interleukin-1beta-induced inflammatory response in human chondrocytes. Arthritis Research & Therapy 13: R93.CrossRefGoogle Scholar
  37. 37.
    Miller, R.E., R.J. Miller, and A.M. Malfait. 2014. Osteoarthritis joint pain: the cytokine connection. Cytokine 70: 185–193.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Jae-Seek You
    • 1
  • In-A Cho
    • 1
  • Kyeong-Rok Kang
    • 1
  • Ji-Su Oh
    • 1
  • Sang-Joun Yu
    • 2
  • Gyeong-Je Lee
    • 3
  • Yo-Seob Seo
    • 4
  • Su-Gwan Kim
    • 1
  • Chun Sung Kim
    • 5
  • Do Kyung Kim
    • 5
  • Hee-Jeong Im
    • 6
  • Jae-Sung Kim
    • 5
    Email author
  1. 1.Department of Oral and Maxillofacial SurgeryChosun UniversityGwangjuRepublic of Korea
  2. 2.Department of PeriodontologyChosun UniversityGwangjuRepublic of Korea
  3. 3.Department of ProsthodonticsChosun UniversityGwangjuRepublic of Korea
  4. 4.Department of Oral and Maxillofacial RadiologyChosun UniversityGwangjuRepublic of Korea
  5. 5.Pre-Dentistry,School of DentistryChosun UniversityGwangjuRepublic of Korea
  6. 6.Department of BiochemistryRush University Medical CenterChicagoUSA

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