期刊论文详细信息
BMC Complementary and Alternative Medicine
Protective effects of biochanin A on articular cartilage: in vitro and in vivo studies
Li Ba1  Qian-hai Ding3  Hui-ming Zhong2  Ding-Qian Wu1 
[1] Research Institute of Emergency Medicine, Jie Fang Road 88#, Hangzhou 310009, People’s Republic of China;Department of Emergency Medicine, The Second Affiliated Hospital of School of Medicine, Zhejiang University, Jie Fang Road 88#, Hangzhou 310009, People’s Republic of China;Department of Orthopedic Surgery, The Second Affiliated Hospital of School of Medicine, Zhejiang University, Jie Fang Road 88#, Hangzhou 310009, People’s Republic of China
关键词: Anterior cruciate ligament transection (ACLT);    Matrix metalloproteinases;    Interleukin-1beta;    Chondroprotection;    Osteoarthritis;    Biochanin A;   
Others  :  1085475
DOI  :  10.1186/1472-6882-14-444
 received in 2014-04-23, accepted in 2014-10-29,  发布年份 2014
PDF
【 摘 要 】

Background

Increased production of matrix metalloproteinases (MMPs) is closely related to the progression of osteoarthritis (OA). The present study was performed to investigate the potential value of biochanin A in inhibition of MMP expression in both rabbit chondrocytes and an animal model of OA.

Methods

MTT assay was performed to assess chondrocyte survival in monolayers. The mRNA and protein expression of MMPs (including MMP-1, MMP-3, and MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in interleukin-1 < beta > (IL-1β)-induced rabbit chondrocytes were determined by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The involvement of the NF-kappaB (NF-κB) pathway activated by IL-1β was determined by western blotting. The in vivo effects of biochanin A were evaluated by intra-articular injection in an experimental OA rabbit model induced by anterior cruciate ligament transection (ACLT).

Results

Biochanin A downregulated the expression of MMPs and upregulated TIMP-1 at both the mRNA and protein levels in IL-1β-induced chondrocytes in a dose-dependent manner. In addition, IL-1β-induced activation of NF-κB was attenuated by biochanin A, as determined by western blotting. Moreover, biochanin A decreased cartilage degradation as determined by both morphological and histological analyses in vivo.

Conclusions

Taken together, these findings suggest that biochanin A may be a useful agent in the treatment and prevention of OA.

【 授权许可】

   
2014 Wu et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150113173715679.pdf 1316KB PDF download
Figure 6. 67KB Image download
Figure 8. 120KB Image download
Figure 7. 35KB Image download
Figure 6. 35KB Image download
Figure 5. 57KB Image download
Figure 4. 43KB Image download
Figure 3. 57KB Image download
Figure 2. 54KB Image download
Figure 1. 37KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

Figure 6.

【 参考文献 】
  • [1]Hunter DJ, Felson DT: Osteoarthritis. BMJ 2006, 332:639-642.
  • [2]Goldring MB, Marcu KB: Cartilage homeostasis in health and rheumatic diseases. Arthritis Res Ther 2009, 11(3):224. BioMed Central Full Text
  • [3]Struglics A, Larsson S, Pratta MA, Kumar S, Lark MW, Lohmander LS: Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments. Osteoarthritis Cartilage 2006, 14:101-113.
  • [4]Burrage PS, Mix KS, Brinckerhoff CE: Matrix metalloproteinases: role in arthritis. Front Biosci 2006, 11:529-543.
  • [5]Woessner JF Jr: MMPs and TIMPs–an historical perspective. Mol Biotechnol 2002, 22:33-49.
  • [6]Goldring SR, Goldring MB: The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res 2004, (427 Suppl):S27-S36.
  • [7]Kobayashi M, Squires GR, Mousa A, Tanzer M, Zukor DJ, Antoniou J, Feige U, Poole AR: Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage. Arthritis Rheum 2005, 52:128-135.
  • [8]Ko WC, Lin LH, Shen HY, Lai CY, Chen CM, Shih CH: Biochanin a, a phytoestrogenic isoflavone with selective inhibition of phosphodiesterase 4, suppresses ovalbumin-induced airway hyperresponsiveness. Evid Based Complement Alternat Med 2011, 2011:635058.
  • [9]Kole L, Giri B, Manna SK, Pal B, Ghosh S: Biochanin-A, an isoflavon, showed anti-proliferative and anti-inflammatory activities through the inhibition of iNOS expression, p38-MAPK and ATF-2 phosphorylation and blocking NFkappaB nuclear translocation. Eur J Pharmacol 2011, 653:8-15.
  • [10]Puli S, Lai JC, Bhushan A: Inhibition of matrix degrading enzymes and invasion in human glioblastoma (U87MG) cells by isoflavones. J Neurooncol 2006, 79:135-142.
  • [11]Syed HM, Green L, Bianski B, Jobe CM, Wongworawat MD: Bupivacaine and triamcinolone may be toxic to human chondrocytes: a pilot study. Clin Orthop Relat Res 2011, 469:2941-2947.
  • [12]Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001, 29:e45.
  • [13]Mankin HJ, Dorfman H, Lippiello L, Zarins A: Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 1971, 53:523-537.
  • [14]Altman RD: Practical considerations for the pharmacologic management of osteoarthritis. Am J Manag Care 2009, 15:S236-S243.
  • [15]Chan FK, Cryer B, Goldstein JL, Lanas A, Peura DA, Scheiman JM, Simon LS, Singh G, Stillman MJ, Wilcox CM, Berger MF, Breazna A, Dodge W: A novel composite endpoint to evaluate the gastrointestinal (GI) effects of nonsteroidal antiinflammatory drugs through the entire GI tract. J Rheumatol 2010, 37:167-174.
  • [16]Hsiao FY, Tsai YW, Huang WF: Changes in physicians’ practice of prescribing cyclooxygenase-2 inhibitor after market withdrawal of rofecoxib: a retrospective study of physician-patient pairs in Taiwan. Clin Ther 2009, 31:2618-2627.
  • [17]Sehdev V, Lai JC, Bhushan A: Biochanin a modulates cell viability, invasion, and growth promoting signaling pathways in HER-2-positive breast cancer cells. J Oncol 2009, 2009:121458.
  • [18]Lee KH, Choi EM: Biochanin A stimulates osteoblastic differentiation and inhibits hydrogen peroxide-induced production of inflammatory mediators in MC3T3-E1 cells. Biol Pharm Bull 2005, 28:1948-1953.
  • [19]Chen HQ, Jin ZY, Li GH: Biochanin A protects dopaminergic neurons against lipopolysaccharide-induced damage through inhibition of microglia activation and proinflammatory factors generation. Neurosci Lett 2007, 417:112-117.
  • [20]Su SJ, Yeh YT, Su SH, Chang KL, Shyu HW, Chen KM, Yeh H: Biochanin a promotes osteogenic but inhibits adipogenic differentiation: evidence with primary adipose-derived stem cells. Evid Base Compl Alternative Med: eCAM 2013, 2013:846039.
  • [21]Tchetina EV: Developmental mechanisms in articular cartilage degradation in osteoarthritis. Arthritis 2011, 2011:683970.
  • [22]Goldring MB: Osteoarthritis and cartilage: the role of cytokines. Curr Rheumatol Rep 2000, 2:459-465.
  • [23]Goldring MB, Otero M, Tsuchimochi K, Ijiri K, Li Y: Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism. Ann Rheum Dis 2008, 67(Suppl 3):iii75-iii82.
  • [24]Pelletier JP, Martel-Pelletier J, Abramson SB: Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum 2001, 44:1237-1247.
  • [25]Chevalier X: Upregulation of enzymatic activity by interleukin-1 in osteoarthritis. Biomed Pharmacother 1997, 51:58-62.
  • [26]Tetlow LC, Adlam DJ, Woolley DE: Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis Rheum 2001, 44:585-594.
  • [27]Westacott CI, Sharif M: Cytokines in osteoarthritis: mediators or markers of joint destruction? Semin Arthritis Rheum 1996, 25:254-272.
  • [28]Huang BD, He AS, Fu M, Sheng PY, Liao WM: Sinomenine suppresses expression of interleukin-1beta-induced matrix metalloproteinases in human osteoarthritic chondrocytes. J Med Plant Res 2010, 4:1830-1836.
  • [29]Toegel S, Wu SQQ, Otero M, Goldring MB, Leelapornpisid P, Chiari C, Kolb A, Unger FM, Windhager R, Viernstein H: Caesalpinia sappan extract inhibits IL1 beta-mediated overexpression of matrix metalloproteinases in human chondrocytes. Genes Nutr 2012, 7:307-318.
  • [30]Klein T, Bischoff R: Physiology and pathophysiology of matrix metalloproteases. Amino Acids 2011, 41:271-290.
  • [31]Heim-Riether A, Taylor SJ, Liang S, Gao DA, Xiong Z, Michael August E, Collins BK, Farmer BT 2nd, Haverty K, Hill-Drzewi M, Junker HD, Mariana Margarit S, Moss N, Neumann T, Proudfoot JR, Keenan LS, Sekul R, Zhang Q, Li J, Farrow NA: Improving potency and selectivity of a new class of non-Zn-chelating MMP-13 inhibitors. Bioorg Med Chem Lett 2009, 19:5321-5324.
  • [32]Hu Y, Xiang JS, DiGrandi MJ, Du X, Ipek M, Laakso LM, Li J, Li W, Rush TS, Schmid J, Skotnicki JS, Tam S, Thomason JR, Wang Q, Levin JI: Potent, selective, and orally bioavailable matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. Bioorg Med Chem 2005, 13:6629-6644.
  • [33]McCawley LJ, Matrisian LM: Matrix metalloproteinases: they’re not just for matrix anymore! Curr Opin Cell Biol 2001, 13:534-540.
  • [34]Jo H, Park JS, Kim EM, Jung MY, Lee SH, Seong SC, Park SC, Kim HJ, Lee MC: The in vitro effects of dehydroepiandrosterone on human osteoarthritic chondrocytes. Osteoarthritis Cartilage / OARS Osteoarthritis Res Soc 2003, 11:585-594.
  • [35]Roman-Blas JA, Jimenez SA: NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage 2006, 14:839-848.
  • [36]Lauder SN, Carty SM, Carpenter CE, Hill RJ, Talamas F, Bondeson J, Brennan P, Williams AS: Interleukin-1beta induced activation of nuclear factor-kappab can be inhibited by novel pharmacological agents in osteoarthritis. Rheumatology (Oxford) 2007, 46:752-758.
  • [37]Marcu KB, Otero M, Olivotto E, Borzi RM, Goldring MB: NF-kappaB signaling: multiple angles to target OA. Curr Drug Targets 2010, 11:599-613.
  • [38]Simmonds RE, Foxwell BM: Signalling, inflammation and arthritis: NF-kappaB and its relevance to arthritis and inflammation. Rheumatology (Oxford) 2008, 47:584-590.
  • [39]Szliszka E, Czuba ZP, Mertas A, Paradysz A, Krol W: The dietary isoflavone biochanin-A sensitizes prostate cancer cells to TRAIL-induced apoptosis. Urol Oncol 2013, 31(3):331-342.
  • [40]Setton LA, Elliott DM, Mow VC: Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration. Osteoarthritis Cartilage 1999, 7:2-14.
  • [41]Laverty S, Girard CA, Williams JM, Hunziker EB, Pritzker KP: The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rabbit. Osteoarthritis Cartilage 2010, 18(Suppl 3):S53-S65.
  • [42]Pickarski M, Hayami T, Zhuo Y, Duong le T: Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. BMC Musculoskelet Disord 2011, 12:197. BioMed Central Full Text
  • [43]Li X, Li J, Cheng K, Lin Q, Wang D, Zhang H, An H, Gao M, Chen A: Effect of low-intensity pulsed ultrasound on MMP-13 and MAPKs signaling pathway in rabbit knee osteoarthritis. Cell Biochem Biophys 2011, 61:427-434.
  文献评价指标  
  下载次数:73次 浏览次数:13次