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Anti-arthritic effects of crocin in interleukin-1β-treated articular chondrocytes and cartilage in a rabbit osteoarthritic model

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Abstract

Objective

Interleukin-1β-mediated production of matrix metalloproteinases (MMPs) plays a pivotal role in the process of osteoarthritis. Crocin, a pharmacologically active component of Crocus sativus L. (saffron), has been used in Chinese traditional medicine. In this study, we aimed to investigate the effects of crocin on MMP-1, MMP-3 and MMP-13 expression in rabbit chondrocytes induced by interleukin-1β (IL-1β) and in an experimental rabbit model induced by anterior cruciate ligament transection.

Methods

Chondrocytes isolated from the articular cartilage of 4-week-old rabbits were cultured and passaged. Confluent chondrocytes were treated with various concentrations of crocin in the presence or absence of IL-1β (10 ng/ml) for 24 h. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting were used to investigate the expression of inducible MMP-1, MMP-3 and MMP-13. In addition, the in-vivo effects of crocin were assessed by morphological and histological analysis.

Results

IL-1β markedly upregulated the expression of MMP-1, -3 and -13 in chondrocytes, and this activation was inhibited by co-incubation with crocin in a dose-dependent manner, in contrast with the control group. Moreover, crocin inhibited IL-1β-induced activation of the nuclear factor kappa B pathway through suppressing degradation of inhibitory-kappa-B-α. In-vivo investigations showed that crocin ameliorated cartilage degeneration and that expression of the MMP-1, -3 and -13 genes in cartilage was significantly inhibited by crocin.

Conclusion

Taken together, our findings suggest that the anti-inflammatory activity of crocin may be of potential value in the prevention and treatment of osteoarthritis.

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References

  1. Feldmann M. Pathogenesis of arthritis: recent research progress. Nat Immunol. 2001;2:771–3.

    Article  PubMed  CAS  Google Scholar 

  2. Kean WF, Kean R, Buchanan WW. Osteoarthritis: symptoms, signs and source of pain. Inflammopharmacology. 2004;12:3–31.

    Article  PubMed  CAS  Google Scholar 

  3. Felson DT. An update on the pathogenesis and epidemiology of osteoarthritis. Radiol Clin North Am. 2004;42:1–9.

    Article  PubMed  Google Scholar 

  4. Takaishi H, Kimura T, Dalal S, Okada Y, D’Armiento J. Joint diseases and matrix metalloproteinases: a role for MMP-13. Curr Pharm Biotechnol. 2008;9:47–54.

    Article  PubMed  CAS  Google Scholar 

  5. Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: role in arthritis. Front Biosci. 2006;11:529–43.

    Article  PubMed  CAS  Google Scholar 

  6. Tardif G, Reboul P, Pelletier JP, Martel-Pelletier J. Ten years in the life of an enzyme: the story of the human MMP-13 (collagenase-3). Mod Rheumatol. 2004;14:197–204.

    Article  PubMed  CAS  Google Scholar 

  7. Aida Y, Maeno M, Suzuki N, Shiratsuchi H, Motohashi M, Matsumura H. The effect of IL-1beta on the expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human chondrocytes. Life Sci. 2005;77:3210–21.

    Article  PubMed  CAS  Google Scholar 

  8. Goldring SR, Goldring MB. The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res 2004;(427 Suppl):S27−36.

  9. Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev. 2004;18:2195–224.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. Tak PP, Firestein GS. NF-kappaB: a key role in inflammatory diseases. J Clin Invest. 2001;107:7–11.

    Article  PubMed  CAS  Google Scholar 

  12. Hosseinzadeh H, Sadeghnia HR, Ghaeni FA, Motamedshariaty VS, Mohajeri SA. Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats. Phytother Res. 2012;26(3):381–6.

    PubMed  CAS  Google Scholar 

  13. Mousavi SH, Tayarani NZ, Parsaee H. Protective effect of saffron extract and crocin on reactive oxygen species-mediated high glucose-induced toxicity in PC12 cells. Cell Mol Neurobiol. 2010;30:185–91.

    Article  PubMed  CAS  Google Scholar 

  14. Papandreou MA, Kanakis CD, Polissiou MG, Efthimiopoulos S, Cordopatis P, Margarity M, et al. Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J Agric Food Chem. 2006;54:8762–8.

    Article  PubMed  CAS  Google Scholar 

  15. Bakshi HA, Sam S, Feroz A, Ravesh Z, Shah GA, Sharma M. Crocin from Kashmiri saffron (Crocus sativus) induces in vitro and in vivo xenograft growth inhibition of Dalton’s lymphoma (DLA) in mice. Asian Pac J Cancer Prev. 2009;10:887–90.

    PubMed  Google Scholar 

  16. Lv CF, Luo CL, Ji HY, Zhao P. Influence of crocin on gene expression profile of human bladder cancer cell lines T24. Zhongguo Zhong Yao Za Zhi. 2008;33:1612–7.

    PubMed  Google Scholar 

  17. He SY, Qian ZY, Tang FT, Wen N, Xu GL, Sheng L. Effect of crocin on experimental atherosclerosis in quails and its mechanisms. Life Sci. 2005;77:907–21.

    Article  PubMed  CAS  Google Scholar 

  18. Sheng L, Qian Z, Zheng S, Xi L. Mechanism of hypolipidemic effect of crocin in rats: crocin inhibits pancreatic lipase. Eur J Pharmacol. 2006;543:116–22.

    Article  PubMed  CAS  Google Scholar 

  19. Lee IA, Lee JH, Baek NI, Kim DH. Antihyperlipidemic effect of crocin isolated from the fructus of Gardenia jasminoides and its metabolite Crocetin. Biol Pharm Bull. 2005;28:2106–10.

    Article  PubMed  CAS  Google Scholar 

  20. Nam KN, Park YM, Jung HJ, Lee JY, Min BD, Park SU, et al. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol. 2010;648:110–6.

    Article  PubMed  CAS  Google Scholar 

  21. Deslauriers AM, Afkhami-Goli A, Paul AM, Bhat RK, Acharjee S, Ellestad KK, et al. Neuroinflammation and endoplasmic reticulum stress are coregulated by crocin to prevent demyelination and neurodegeneration. J Immunol. 2011;187:4788–99.

    Article  PubMed  CAS  Google Scholar 

  22. Ghadrdoost B, Vafaei AA, Rashidy-Pour A, Hajisoltani R, Bandegi AR, Motamedi F, et al. Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. Eur J Pharmacol. 2011;667:222–9.

    Article  PubMed  CAS  Google Scholar 

  23. Mehri S, Abnous K, Mousavi SH, Shariaty VM, Hosseinzadeh H. Neuroprotective effect of crocin on acrylamide-induced cytotoxicity in PC12 cells. Cell Mol Neurobiol. 2012;32(2):227–35.

    Article  PubMed  CAS  Google Scholar 

  24. Lieberthal W, Triaca V, Koh JS, Pagano PJ, Levine JS. Role of superoxide in apoptosis induced by growth factor withdrawal. Am J Physiol. 1998;275:F691–702.

    PubMed  CAS  Google Scholar 

  25. Livak KJ, Schmittgen TD. Analysis of Relative Gene Expression Data Using Real- Time Quantitative PCR and the 2 T Method. Methods 2001; 25:402–408.

    Google Scholar 

  26. Jo H, Ahn HJ, Kim EM, Kim HJ, Seong SC, Lee I, et al. Effects of dehydroepiandrosterone on articular cartilage during the development of osteoarthritis. Arthritis Rheum. 2004;50:2531–8.

    Article  PubMed  CAS  Google Scholar 

  27. 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;53:523–37.

    PubMed  CAS  Google Scholar 

  28. Vincenti MP, Brinckerhoff CE. Transcriptional regulation of collagenase (MMP-1, MMP-13) genes in arthritis: integration of complex signaling pathways for the recruitment of gene-specific transcription factors. Arthritis Res. 2002;4(3):157–64.

    Article  PubMed  CAS  Google Scholar 

  29. Jo H, Park JS, Kim EM, Jung MY, Lee SH, Seong SC, et al. The in vitro effects of dehydroepiandrosterone on human osteoarthritic chondrocytes. Osteoarthr Cartil. 2003;11:585–94.

    Article  PubMed  CAS  Google Scholar 

  30. 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;44:585–94.

    Article  PubMed  CAS  Google Scholar 

  31. Ishiguro N, Ito T, Ito H, Iwata H, Jugessur H, Ionescu M, et al. Relationship of matrix metalloproteinases and their inhibitors to cartilage proteoglycan and collagen turnover: analyses of synovial fluid from patients with osteoarthritis. Arthritis Rheum. 1999;42:129–36.

    Article  PubMed  CAS  Google Scholar 

  32. Lohmander LS, Brandt KD, Mazzuca SA, Katz BP, Larsson S, Struglics A, et al. Use of the plasma stromelysin (matrix metalloproteinase 3) concentration to predict joint space narrowing in knee osteoarthritis. Arthritis Rheum. 2005;52:3160–7.

    Article  PubMed  CAS  Google Scholar 

  33. Skotnicki JS, DiGrandi MJ, Levin JI. Design strategies for the identification of MMP-13 and Tace inhibitors. Curr Opin Drug Discov Devel. 2003;6:742–59.

    PubMed  CAS  Google Scholar 

  34. Goldring MB, Otero M, Plumb DA, Dragomir C, Favero M, El Hachem K, et al. Roles of inflammatory and anabolic cytokines in cartilage metabolism: signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. Eur Cell Mater. 2011;21:202–20.

    PubMed  CAS  Google Scholar 

  35. Malemud CJ. Anticytokine therapy for osteoarthritis: evidence to date. Drugs Aging. 2010;27:95–115.

    Article  PubMed  CAS  Google Scholar 

  36. Daheshia M, Yao JQ. The interleukin 1beta pathway in the pathogenesis of osteoarthritis. J Rheumatol. 2008;35:2306–12.

    Article  PubMed  CAS  Google Scholar 

  37. Blom AB, van der Kraan PM, van den Berg WB. Cytokine targeting in osteoarthritis. Curr Drug Targets. 2007;8:283–92.

    Article  PubMed  CAS  Google Scholar 

  38. Makarov SS. NF-kappaB as a therapeutic target in chronic inflammation: recent advances. Mol Med Today. 2000;6:441–8.

    Article  PubMed  CAS  Google Scholar 

  39. Roman-Blas JA, Jimenez SA. NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage. 2006;14:839–48.

    Article  PubMed  CAS  Google Scholar 

  40. Xu GL, Li G, Ma HP, Zhong H, Liu F, Ao GZ. Preventive effect of crocin in inflamed animals and in LPS-challenged RAW 264.7 cells. J Agric Food Chem. 2009;57:8325–30.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (81071492), the National Natural Science Foundation of China (81101377, 81171687), the Zhejiang Provincial Natural Science Foundation of China (Y2100161, Y2090283) and the Scientific Research Fund of Zhejiang Provincial Education Department (Y201018936).

Conflict of interest

The authors have declared no conflict of interest.

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Authors and Affiliations

  1. 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

    Qianhai Ding, Huiming Zhong, Yiying Qi, Ye Cheng, Weijun Li, Shigui Yan & Xianghua Wang

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  1. Qianhai Ding
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  2. Huiming Zhong
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  3. Yiying Qi
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  4. Ye Cheng
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  6. Shigui Yan
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  7. Xianghua Wang
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Correspondence to Xianghua Wang.

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Responsible Editor: Liwu Li.

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Ding, Q., Zhong, H., Qi, Y. et al. Anti-arthritic effects of crocin in interleukin-1β-treated articular chondrocytes and cartilage in a rabbit osteoarthritic model. Inflamm. Res. 62, 17–25 (2013). https://doi.org/10.1007/s00011-012-0546-3

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  • DOI: https://doi.org/10.1007/s00011-012-0546-3

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