Coumestrol Counteracts Interleukin-1β-Induced Catabolic Effects by Suppressing Inflammation in Primary Rat Chondrocytes
- 405 Downloads
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 WORDSosteoarthritis inflammation chondrocyte coumestrol anti-catabolic effects
This study was supported by research fund from Chosun University Dental Hospital, 2015.
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.
- 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
- 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
- 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
- 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.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
- 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
- 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
- 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