Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Chondroprotective Effects of Wogonin in Experimental Models of Osteoarthritis in vitro and in vivo

  • Park, Jin Sung (Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Lee, Hyun Jae (Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Lee, Dong Yeong (Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Jo, Ho Seung (Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Jeong, Jin Hoon (Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Kim, Dong Hee (Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Nam, Dae Cheol (Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University) ;
  • Lee, Choong Jae (Department of Pharmacology, School of Medicine, Chungnam National University) ;
  • Hwang, Sun-Chul (Department of Orthopedic Surgery and Institute of Health Sciences, School of Medicine and Hospital, Gyeongsang National University)
  • Received : 2015.04.23
  • Accepted : 2015.06.09
  • Published : 2015.09.01
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Abstract

We evaluated the chondroprotective effects of wogonin by investigating its effects on the gene expression and production of matrix metalloproteinase-3 (MMP-3) in primary cultured rabbit articular chondrocytes, as well as on production of MMP-3 in the rat knee. Rabbit articular chondrocytes were cultured in a monolayer, and RT-PCR was used to measure interleukin-$1{\beta}$ (IL-$1{\beta}$)-induced expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), and type II collagen. In rabbit articular chondrocytes, the effects of wogonin on IL-$1{\beta}$-induced production and proteolytic activity of MMP-3 were investigated using western blot analysis and casein zymography, respectively. The effect of wogonin on MMP-3 protein production was also examined in vivo. In rabbit articular chondrocytes, wogonin inhibited the expression of MMP-3, MMP-1, MMP-13, and ADAMTS-4, but increased expression of type II collagen. Furthermore, wogonin inhibited the production and proteolytic activity of MMP-3 in vitro, and inhibited production of MMP-3 protein in vivo. These results suggest that wogonin can regulate the gene expression and production of MMP-3, by directly acting on articular chondrocytes.

Keywords

References

  1. Aida, Y., Maeno, M., Suzuki, N., Shiratsuchi, H., Motohashi, M. and Matsumura, H. (2005) The effect of IL-1beta on the expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human chondrocytes. Life Sci. 77, 3210-3221. https://doi.org/10.1016/j.lfs.2005.05.052
  2. Aigner, T. and McKenna, L. (2002) Molecular pathology and pathobiology of osteoarthritic cartilage. Cell. Mol. Life Sci. 59, 5-18. https://doi.org/10.1007/s00018-002-8400-3
  3. Birkedal-Hansen, H., Moore, W. G. and Bodden, M. K. (1993) Matrix metalloproteinases: a review. Crit. Rev. Oral Biol. Med. 4, 197-250.
  4. Bonnet, C. S. and Walsh, D. A. (2005) Osteoarthritis, angiogenesis and inflammation. Rheumatology 44, 7-16. https://doi.org/10.1093/rheumatology/keh344
  5. Burrage, P. S., Mix, K. S. and Brinckerhoff, C. E. (2006) Matrix metalloproteinases: role in arthritis. Front. Biosci. 11, 529-543. https://doi.org/10.2741/1817
  6. Dean, D. D., Martel-Pelletier, J., Pelletier, J. P., Howell, D. S. and Woessner, J. F. Jr. (1989) Evidence for metalloproteinase and metalloproteinase inhibitor imbalance in human osteoarthritic cartilage. J. Clin. Invest. 84, 678-685. https://doi.org/10.1172/JCI114215
  7. Echtermeyer, F., Bertrand, J. and Dreier, R. (2009) Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in osteoarthritis. Nat. Med. 15, 1072-1076. https://doi.org/10.1038/nm.1998
  8. Freemont, A. J., Hampson, V., Tilman, R., Goupille, P., Taiwo, Y. and Hoyland, J. A. (1997) Gene expression of matrix metalloproteinases 1, 3, and 9 by chondrocytes in osteoarthritic human knee articular cartilage is zone and grade specific. Ann. Rheum. Dis. 56, 542-549. https://doi.org/10.1136/ard.56.9.542
  9. Garnero, P., Rousseau, J. C. and Delmas. P. D. (2000) Molecular basis and clinical use of biochemical markers of bone, cartilage, and synovium in joint diseases. Arthritis Rheum. 43, 953-968. https://doi.org/10.1002/1529-0131(200005)43:5<953::AID-ANR1>3.0.CO;2-Q
  10. Goldring, M. B., Otero, M., Tsuchimochi, K., Ijiri, K. and Li, Y. (2008) Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism. Ann. Rheum. Dis. 67 (Suppl 3), iii75-iii82.
  11. Goupille, P., Jayson, M. I., Valat, J. P. and Freemont, A. J. (1998) Matrix metalloproteinases: the clue to intervertebral disc degeneration. Spine (Phila Pa 1976) 23, 1612-1626. https://doi.org/10.1097/00007632-199807150-00021
  12. Hu, P. F., Chen, W. P., Tang, J. L., Bao, J. P. and Wu, L. D. (2011) Protective effects of berberine in an experimental rat osteoarthritis model. Phytother. Res. 25, 878-885. https://doi.org/10.1002/ptr.3359
  13. Jo, H., Park, J. S. and Kim, E. M. (2003) The in vitro effects of dehydroepiandrosterone on human osteoarthritic chondrocytes. Osteoarthritis Cartilage 11, 585-594. https://doi.org/10.1016/S1063-4584(03)00094-3
  14. Kanyama, M., Kuboki, T. and Kojima, S. (2000) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids of patients with temporomandibular joint osteoarthritis. J. Orofac. Pain 14, 20-30.
  15. Kimura, Y. and Sumiyoshi, M. (2013) Anti-tumor and anti-metastatic actions of wogonin isolated from Scutellaria baicalensis roots through anti-lymphangiogenesis. Phytomedicine 20, 328-336. https://doi.org/10.1016/j.phymed.2012.10.016
  16. Kobayashi, M., Squires, G. R. and Mousa, A. (2005) Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage. Arthritis Rheum. 52, 128-135. https://doi.org/10.1002/art.20776
  17. Kullich, W., Fagerer, N. and Schwann, H. (2007) Effect of the NSAID nimesulide on the radical scavenger glutathione S-transferase in patients with osteoarthritis of the knee. Curr. Med. Res. Opin. 23, 1981-1986. https://doi.org/10.1185/030079907X223486
  18. Kwak, S., Ku, S. K., Han, M. S. and Bae, J. S. (2014) Vascular barrier protective effects of baicalin, baicalein and wogonin in vitro and in vivo. Toxicol. Appl. Pharmacol. 281, 30-38. https://doi.org/10.1016/j.taap.2014.09.003
  19. Lee, S. O., Jeong, Y. J., Yu, M. H., Lee, J. W., Hwangbo, M. H., Kim, C. H. and Lee, I. S. (2006) Wogonin suppresses TNF-alpha-induced MMP-9 expression by blocking the NF-kappaB activation via MAPK signaling pathways in human aortic smooth muscle cells. Biochem. Biophys. Res. Commun. 351, 118-125. https://doi.org/10.1016/j.bbrc.2006.10.006
  20. Lee, W., Ku, S. K. and Bae, J. S. (2015) Anti-inflammatory effects of Baicalin, Baicalein, and Wogonin in vitro and in vivo. Inflammation 38, 110-125. https://doi.org/10.1007/s10753-014-0013-0
  21. Lijnen, H. R. (2002) Matrix metalloproteinases and cellular fibrinolytic proteolytic activity. Biochemistry 67, 92-98.
  22. Lim, H., Park, H. and Kim, H. P. (2011) Effects of flavonoids on matrix metalloproteinase-13 expression of interleukin-1${\beta}$-treated articular chondrocytes and their cellular mechanisms: inhibition of c-Fos/AP-1 and JAK/STAT signaling pathways. J. Pharmacol. Sci. 116, 221-231. https://doi.org/10.1254/jphs.11014FP
  23. Lin, C. M., Chang, H., Chen, Y. H., Li, S. Y., Wu, I. H. and Chiu, J. H. (2006) Protective role of wogonin against lipopolysaccharideinduced angiogenesis via VEGFR-2, not VEGFR-1. Int. Immunopharmacol 6, 1690-1698. https://doi.org/10.1016/j.intimp.2006.07.003
  24. Lin, P. M., Chen, C. T. and Torzilli, P. A. (2004) Increased stromelysin-1 (MMP-3), proteoglycan degradation (3B3- and 7D4) and collagen damage in cyclically load-injured articular cartilage. Osteoarthritis Cartilage 12, 485-496. https://doi.org/10.1016/j.joca.2004.02.012
  25. Little, C. B., Barai, A. and Burkhardt, D. (2009) Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum. 60, 3723-3733. https://doi.org/10.1002/art.25002
  26. Loeser, R. F. (2006) Molecular mechanisms of cartilage destruction: mechanics, inflammatory mediators and aging collide. Arthritis Rheum. 54, 1357-1360. https://doi.org/10.1002/art.21813
  27. Mankin, H. J. (1982) The response for articular cartilage to mechanical injury. J. Bone Joint Surg. Am. 64, 460-466.
  28. Moon, P. D., Jeong, H. S., Chun, C. S. and Kim, H. M. (2011) Baekjeolyusin-tang and its active component berberine block the release of collagen and proteoglycan from IL-$1{\beta}$-stimulated rabbit cartilage and down-regulate matrix metalloproteinases in rabbit chondrocytes. Phytother. Res. 25, 844-850. https://doi.org/10.1002/ptr.3353
  29. Neuhold, L. A., Killar, L. and Zhao, W. (2001) Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice. J. Clin. Invest. 107, 35-44. https://doi.org/10.1172/JCI10564
  30. Pantsulaia, I., Kalichman, L. and Kobyliansky, E. (2010) Association between radiographic hand osteoarthritis and RANKL, OPG and inflammatory markers. Osteoarthritis Cartilage 18, 1448-1453. https://doi.org/10.1016/j.joca.2010.06.009
  31. Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S. and Boyd, M. R. (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst. 82, 1107-1112. https://doi.org/10.1093/jnci/82.13.1107
  32. Stanton, H., Rogerson, F. M. and East, C. J. (2005) ADAMTS-5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature. 434, 648-652. https://doi.org/10.1038/nature03417
  33. Yoshihara, Y., Nakamura, H. and Obata, K. (2000) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann. Rheum. Dis. 59, 455-461. https://doi.org/10.1136/ard.59.6.455

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