Abstract
Tenuigenin (TEN), the main active component of Polygala tenuifolia, has been reported to have anti-inflammatory effects. However, the effects of TEN on IL-1β-stimulated osteoarthritis chondrocytes have not been reported. The purpose of this study was to investigate the anti-inflammatory effects and mechanism of TEN on IL-1β-stimulated human osteoarthritis chondrocytes. Human osteoarthritis chondrocytes were pretreated with or without TEN for 1 h and then stimulated with IL-1β. The production of NO and PGE2 were detected by the Griess reagent and ELISA. The expression of NF-κB and MAPKs (p38, JNK, ERK) were measured by Western blot analysis. The production of MMP-1, MMP3, and MMP13 were measured by ELISA. The results showed that treatment of TEN significantly inhibited IL-1β-induced NO and PGE2 production. TEN also suppressed IL-1β-induced MMP-1, MMP3, and MMP13 expression. Furthermore, TEN was found to inhibit IL-1β-induced NF-κB activation, PI3K, and AKT phosphorylation. In conclusion, these results suggest that TEN inhibits IL-1β-induced inflammation in human osteoarthritis chondrocytes by inhibiting PI3K/AKT/NF-κB signaling pathway.
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References
Benito, M.J., D.J. Veale, O. FitzGerald, W.B. van den Berg, and B. Bresnihan. 2005. Synovial tissue inflammation in early and late osteoarthritis. Annals of the Rheumatic Diseases 64: 1263–1267.
Pelletier, J.P., J. Martel‐Pelletier, and S.B. Abramson. 2001. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis & Rheumatism 44: 1237–1247.
Pelletier, J.-P., F. Mineau, P. Ranger, G. Tardif, and J. Martel-Pelletier. 1996. The increased synthesis of inducible nitric oxide inhibits IL-1ra synthesis by human articular chondrocytes: possible role in osteoarthritic cartilage degradation. Osteoarthritis and Cartilage 4: 77–84.
Kobayashi, M., G.R. Squires, A. Mousa, M. Tanzer, D.J. Zukor, J. Antoniou, U. Feige, and A.R. Poole. 2005. Role of interleukin‐1 and tumor necrosis factor α in matrix degradation of human osteoarthritic cartilage. Arthritis & Rheumatism 52: 128–135.
Kapoor, M., J. Martel-Pelletier, D. Lajeunesse, J.-P. Pelletier, and H. Fahmi. 2011. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nature Reviews. Rheumatology 7: 33–42.
Amin, A.R., M. Dave, M. Attur, and S.B. Abramson. 2000. COX-2, NO, and cartilage damage and repair. Current Rheumatology Reports 2: 447–453.
Yang, G., H.-J. Im, and J.H.-C. Wang. 2005. Repetitive mechanical stretching modulates IL-1β induced COX-2, MMP-1 expression, and PGE 2 production in human patellar tendon fibroblasts. Gene 363: 166–172.
Burrage, P.S., K.S. Mix, and C.E. Brinckerhoff. 2006. Matrix metalloproteinases: role in arthritis. Frontiers in Bioscience 11: 529–543.
Silverstein, F.E., G. Faich, J.L. Goldstein, L.S. Simon, T. Pincus, A. Whelton, R. Makuch, G. Eisen, N.M. Agrawal, and W.F. Stenson. 2000. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. JAMA 284: 1247–1255.
Liang, Z., F. Shi, Y. Wang, L. Lu, Z. Zhang, X. Wang, and X. Wang. 2011. Neuroprotective effects of tenuigenin in a SH-SY5Y cell model with 6-OHDA-induced injury. Neuroscience Letters 497: 104–109.
Yuan, H.L., B. Li, J. Xu, Y. Wang, Y. He, Y. Zheng, and X.M. Wang. 2012. Tenuigenin protects dopaminergic neurons from inflammation‐mediated damage induced by the lipopolysaccharide. CNS Neuroscience & Therapeutics 18: 584–590.
Cai, Z.-L., C.-Y. Wang, X.-Y. Gu, N.-J. Wang, J.-J. Wang, W.-X. Liu, P. Xiao, and C.-H. Li. 2013. Tenuigenin ameliorates learning and memory impairments induced by ovariectomy. Physiology & Behavior 118: 112–117.
Chen, Y., X. Huang, W. Chen, N. Wang, and L. Li. 2012. Tenuigenin promotes proliferation and differentiation of hippocampal neural stem cells. Neurochemical Research 37: 771–777.
Lv H, Zhu C, Liao Y, Gao Y, Lu G, Zhong W, Zheng Y, Chen W, Ci X. 2015. Tenuigenin ameliorates acute lung injury by inhibiting NF-κB and MAPK signalling pathways. Respiratory Physiology & Neurobiology 216: 43–51.
Cheng, A.W., T.V. Stabler, M. Bolognesi, and V.B. Kraus. 2011. Selenomethionine inhibits IL-1beta inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) expression in primary human chondrocytes. Osteoarthritis and Cartilage 19: 118–125.
Fukui, N., Y. Zhu, W.J. Maloney, J. Clohisy, and L.J. Sandell. 2003. Stimulation of BMP-2 expression by pro-inflammatory cytokines IL-1 and TNF-α in normal and osteoarthritic chondrocytes. The Journal of Bone & Joint Surgery 85: 59–66.
Daheshia, M., and J.Q. Yao. 2008. The interleukin 1β pathway in the pathogenesis of osteoarthritis. The Journal of Rheumatology 35: 2306–2312.
Jacques, C., M. Gosset, F. Berenbaum, and C. Gabay. 2006. The role of IL‐1 and IL‐1Ra in joint inflammation and cartilage degradation. Vitamins & Hormones 74: 371–403.
Goldring, M.B., and F. Berenbaum. 2004. The regulation of chondrocyte function by proinflammatory mediators: prostaglandins and nitric oxide. Clinical Orthopaedics and Related Research 427: S37–S46.
Studer, R., D. Jaffurs, M. Stefanovic-Racic, P. Robbins, and C. Evans. 1999. Nitric oxide in osteoarthritis. Osteoarthritis and Cartilage 7: 377–379.
Futani, H., A. Okayama, K. Matsui, S. Kashiwamura, T. Sasaki, T. Hada, K. Nakanishi, H. Tateishi, S. Maruo, and H. Okamura. 2002. Relation between interleukin-18 and PGE2 in synovial fluid of osteoarthritis: a potential therapeutic target of cartilage degradation. Journal of Immunotherapy 25: S61–S64.
Karan, A., M.A. Karan, P. Vural, N. Erten, C. Taşçıoğlu, C. Aksoy, M. Canbaz, and A. Öncel. 2003. Synovial fluid nitric oxide levels in patients with knee osteoarthritis. Clinical Rheumatology 22: 397–399.
Koskinen, A., K. Vuolteenaho, R. Nieminen, T. Moilanen, and E. Moilanen. 2010. Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients. Clinical and Experimental Rheumatology 29: 57–64.
Baker, R.G., M.S. Hayden, and S. Ghosh. 2011. NF-κB, inflammation, and metabolic disease. Cell Metabolism 13: 11–22.
Lawrence, T., and C. Fong. 2010. The resolution of inflammation: anti-inflammatory roles for NF-κB. The International Journal of Biochemistry & Cell Biology 42: 519–523.
Roman-Blas, J., and S. Jimenez. 2006. NF-κB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis and Cartilage 14: 839–848.
Jeong JW, Lee HH, Choi EO, Lee KW, Kim KY, Kim SG, Hong SH, Kim GY, Park C, Kim HK, et al. 2015. Schisandrae Fructus inhibits IL-1beta-induced matrix metalloproteinases and inflammatory mediators production in SW1353 human chondrocytes by suppressing NF-kappaB and MAPK activation. Drug Development Research 76: 474–483.
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Wang, C., Zeng, L., Zhang, T. et al. Tenuigenin Prevents IL-1β-induced Inflammation in Human Osteoarthritis Chondrocytes by Suppressing PI3K/AKT/NF-κB Signaling Pathway. Inflammation 39, 807–812 (2016). https://doi.org/10.1007/s10753-016-0309-3
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DOI: https://doi.org/10.1007/s10753-016-0309-3