Annals of the New York Academy of Sciences2009; 1171; 428-435; doi: 10.1111/j.1749-6632.2009.04687.x

Interleukin-1beta-induced extracellular matrix degradation and glycosaminoglycan release is inhibited by curcumin in an explant model of cartilage inflammation.

Abstract: Osteoarthritis (OA) is a degenerative and inflammatory disease of synovial joints that is characterized by the loss of articular cartilage, for which there is increasing interest in natural remedies. Curcumin (diferuloylmethane) is the main polyphenol in the spice turmeric, derived from rhizomes of the plant Curcuma longa. Curcumin has potent chemopreventive properties and has been shown to inhibit nuclear factor kappaB-mediated inflammatory signaling in many cell types, including chondrocytes. In this study, normal articular cartilage was harvested from metacarpophalangeal and metatarsophalangeal joints of eight horses, euthanized for reasons other than research purposes, to establish an explant model mimicking the inflammatory events that occur in OA. Initially, cartilage explants (N= 8) were stimulated with increasing concentrations of the proinflammatory cytokine IL-1beta to select effective doses for inducing cartilage degeneration in the explant model. Separate cartilage explants were then cotreated with IL-1beta at either 10 ng/mL (n= 3) or 25 ng/mL (n= 3) and curcumin (0.1 micromol/L, 0.5 micromol/L, 1 micromol/L, 10 micromol/L, and 100 micromol/L). After 5 days, the percentage of glycosaminoglycan (GAG) release from the explants was assessed using a dimethylmethylene blue colorimetric assay. Curcumin (100 micromol/L) significantly reduced IL-1beta-stimulated GAG release in the explants by an average of 20% at 10 ng/mL and 27% at 25 ng/mL back to unstimulated control levels (P < 0.001). Our results suggest that this explant model effectively simulates the proinflammatory cytokine-mediated release of articular cartilage components seen in OA. Furthermore, the evidence suggests that the inflammatory cartilage explant model is useful for studying the effects of curcumin on inflammatory pathways and gene expression in IL-1beta-stimulated chondrocytes.
Publication Date: 2009-09-03 PubMed ID: 19723086DOI: 10.1111/j.1749-6632.2009.04687.xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article examines the beneficial effect of curcumin (main polyphenol in turmeric) on osteoarthritis (OA) by inhibiting inflammation and degradation in the cartilage. The study uses an explant model to emulate the inflammation occurring in OA.

Experiment Design

  • The study employs normal articular cartilage harvested from the joints of eight horses that were euthanized for non-research purposes. The harvested cartilages were used to create an explant model simulating the inflammatory events in OA.
  • Initially, the cartilage explants were exposed to escalating concentrations of the proinflammatory cytokine, IL-1beta, to identify effective doses that would induce cartilage degeneration in the model.
  • Upon establishing the effective doses, other cartilages were treated with IL-1beta at different concentrations (10 ng/mL or 25 ng/mL) and combined with various curcumin concentrations (0.1 micromol/L to 100 micromol/L).

Procedure and Results

  • The cartilages were observed for 5 days, after which the amount of glycosaminoglycan (GAG) release from the explants was estimated using a colorimetric assay, dimethylmethylene blue.
  • It was found that curcumin at a concentration of 100 micromol/L notably reduced the release of GAG stimulated by IL-1beta by an average of 20% at 10 ng/mL and 27% at 25 ng/mL, bringing it back to unstimulated control levels.

Conclusion and Implications

  • The results highlight that the in-vitro explant model effectively simulates the inflammatory cytokine-mediated processes of cartilage destruction seen in OA.
  • Clinically, it showcases the potential of curcumin in mitigating OA inflammation by inhibiting the inflammatory pathways and gene expression in cartilage cells (chondrocytes) stimulated with IL-1beta.
  • This study suggests that exploiting natural remedies like curcumin can pave the way for effective countermeasures against OA.

Cite This Article

APA
Clutterbuck AL, Mobasheri A, Shakibaei M, Allaway D, Harris P. (2009). Interleukin-1beta-induced extracellular matrix degradation and glycosaminoglycan release is inhibited by curcumin in an explant model of cartilage inflammation. Ann N Y Acad Sci, 1171, 428-435. https://doi.org/10.1111/j.1749-6632.2009.04687.x

Publication

ISSN: 1749-6632
NlmUniqueID: 7506858
Country: United States
Language: English
Volume: 1171
Pages: 428-435

Researcher Affiliations

Clutterbuck, Abigail L
  • Division of Veterinary Medicine, School of Veterinary Medicine and Science, University of Nottingham, Leicestershire, United Kingdom. Abigail.Clutterbuck@nottingham.ac.uk
Mobasheri, Ali
    Shakibaei, Mehdi
      Allaway, David
        Harris, Pat

          MeSH Terms

          • Animals
          • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
          • Cartilage / drug effects
          • Cartilage / metabolism
          • Cartilage / pathology
          • Curcumin / pharmacology
          • Dose-Response Relationship, Drug
          • Extracellular Matrix / metabolism
          • Glycosaminoglycans / metabolism
          • Horses
          • Insulin-Like Growth Factor I / pharmacology
          • Interleukin-1beta / toxicity
          • Metacarpophalangeal Joint / drug effects
          • Metacarpophalangeal Joint / metabolism
          • Metacarpophalangeal Joint / pathology
          • Osteoarthritis / chemically induced
          • Osteoarthritis / metabolism
          • Osteoarthritis / prevention & control
          • Tissue Culture Techniques

          Grant Funding

          • BBSRC/S/M/2006/13141 / Biotechnology and Biological Sciences Research Council

          Citations

          This article has been cited 32 times.
          1. Patnaik R, Jannati S, Sivani BM, Rizzo M, Naidoo N, Banerjee Y. Efficient Generation of Chondrocytes From Bone Marrow-Derived Mesenchymal Stem Cells in a 3D Culture System: Protocol for a Practical Model for Assessing Anti-Inflammatory Therapies.. JMIR Res Protoc 2023 Jul 28;12:e42964.
            doi: 10.2196/42964pubmed: 37505889google scholar: lookup
          2. Ashruf OS, Ansari MY. Natural Compounds: Potential Therapeutics for the Inhibition of Cartilage Matrix Degradation in Osteoarthritis.. Life (Basel) 2022 Dec 30;13(1).
            doi: 10.3390/life13010102pubmed: 36676051google scholar: lookup
          3. Keller LE, Tait Wojno ED, Begum L, Fortier LA. Regulatory T cells provide chondroprotection through increased TIMP1, IL-10 and IL-4, but cannot mitigate the catabolic effects of IL-1u03b2 and IL-6 in a tri-culture model of osteoarthritis.. Osteoarthr Cartil Open 2021 Sep;3(3):100193.
            doi: 10.1016/j.ocarto.2021.100193pubmed: 36474817google scholar: lookup
          4. Han G, Zhang Y, Li H. The Combination Treatment of Curcumin and Probucol Protects Chondrocytes from TNF-u03b1 Induced Inflammation by Enhancing Autophagy and Reducing Apoptosis via the PI3K-Akt-mTOR Pathway.. Oxid Med Cell Longev 2021;2021:5558066.
            doi: 10.1155/2021/5558066pubmed: 34257809google scholar: lookup
          5. Spinnen J, Shopperly LK, Rendenbach C, Ku00fchl AA, Sentu00fcrk U, Kendoff D, Hemmati-Sadeghi S, Sittinger M, Dehne T. A Novel Method Facilitating the Simple and Low-Cost Preparation of Human Osteochondral Slice Explants for Large-Scale Native Tissue Analysis.. Int J Mol Sci 2021 Jun 15;22(12).
            doi: 10.3390/ijms22126394pubmed: 34203791google scholar: lookup
          6. Sukhikh S, Noskova S, Ivanova S, Ulrikh E, Izgaryshev A, Babich O. Chondroprotection and Molecular Mechanism of Action of Phytonutraceuticals on Osteoarthritis.. Molecules 2021 Apr 20;26(8).
            doi: 10.3390/molecules26082391pubmed: 33924083google scholar: lookup
          7. Yabas M, Orhan C, Er B, Tuzcu M, Durmus AS, Ozercan IH, Sahin N, Bhanuse P, Morde AA, Padigaru M, Sahin K. A Next Generation Formulation of Curcumin Ameliorates Experimentally Induced Osteoarthritis in Rats via Regulation of Inflammatory Mediators.. Front Immunol 2021;12:609629.
            doi: 10.3389/fimmu.2021.609629pubmed: 33776996google scholar: lookup
          8. Houtman E, van Hoolwerff M, Lakenberg N, Suchiman EHD, van der Linden-van der Zwaag E, Nelissen RGHH, Ramos YFM, Meulenbelt I. Human Osteochondral Explants: Reliable Biomimetic Models to Investigate Disease Mechanisms and Develop Personalized Treatments for Osteoarthritis.. Rheumatol Ther 2021 Mar;8(1):499-515.
            doi: 10.1007/s40744-021-00287-ypubmed: 33608843google scholar: lookup
          9. Mehta S, Young CC, Warren MR, Akhtar S, Shefelbine SJ, Crane JD, Bajpayee AG. Resveratrol and Curcumin Attenuate Ex Vivo Sugar-Induced Cartilage Glycation, Stiffening, Senescence, and Degeneration.. Cartilage 2021 Dec;13(2_suppl):1214S-1228S.
            doi: 10.1177/1947603520988768pubmed: 33472415google scholar: lookup
          10. Buhrmann C, Honarvar A, Setayeshmehr M, Karbasi S, Shakibaei M, Valiani A. Herbal Remedies as Potential in Cartilage Tissue Engineering: An Overview of New Therapeutic Approaches and Strategies.. Molecules 2020 Jul 6;25(13).
            doi: 10.3390/molecules25133075pubmed: 32640693google scholar: lookup
          11. Ma W, Wang S, Xu H, Xie W, Bi R. The effect of curcuminoids for treating knee osteoarthritis: A protocol for systematic review and meta analysis.. Medicine (Baltimore) 2020 Jun 19;99(25):e20556.
            doi: 10.1097/MD.0000000000020556pubmed: 32569177google scholar: lookup
          12. Jiang C, Luo P, Li X, Liu P, Li Y, Xu J. Nrf2/ARE is a key pathway for curcumin-mediated protection of TMJ chondrocytes from oxidative stress and inflammation.. Cell Stress Chaperones 2020 May;25(3):395-406.
            doi: 10.1007/s12192-020-01079-zpubmed: 32124251google scholar: lookup
          13. Guo Y, Tian L, Du X, Deng Z. MiR-203 regulates estrogen receptor u03b1 and cartilage degradation in IL-1u03b2-stimulated chondrocytes.. J Bone Miner Metab 2020 May;38(3):346-356.
            doi: 10.1007/s00774-019-01062-4pubmed: 31894489google scholar: lookup
          14. Pearson W, Kott LS. A biological extract of turmeric (Curcuma longa) modulates response of cartilage explants to lipopolysaccharide.. BMC Complement Altern Med 2019 Sep 11;19(1):252.
            doi: 10.1186/s12906-019-2660-zpubmed: 31506082google scholar: lookup
          15. Kim L, Kim JY. Chondroprotective effect of curcumin and lecithin complex in human chondrocytes stimulated by IL-1u03b2 via an anti-inflammatory mechanism.. Food Sci Biotechnol 2019 Apr;28(2):547-553.
            doi: 10.1007/s10068-018-0470-6pubmed: 30956867google scholar: lookup
          16. Mata M, Milian L, Oliver M, Zurriaga J, Sancho-Tello M, de Llano JJM, Carda C. In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study.. Stem Cells Int 2017;2017:8309256.
            doi: 10.1155/2017/8309256pubmed: 28951745google scholar: lookup
          17. Niazvand F, Khorsandi L, Abbaspour M, Orazizadeh M, Varaa N, Maghzi M, Ahmadi K. Curcumin-loaded poly lactic-co-glycolic acid nanoparticles effects on mono-iodoacetate -induced osteoarthritis in rats.. Vet Res Forum 2017 Spring;8(2):155-161.
            pubmed: 28785392
          18. Wang J, Ma J, Gu JH, Wang FY, Shang XS, Tao HR, Wang X. Regulation of type II collagen, matrix metalloproteinase-13 and cell proliferation by interleukin-1u03b2 is mediated by curcumin via inhibition of NF-u03baB signaling in rat chondrocytes.. Mol Med Rep 2017 Aug;16(2):1837-1845.
            doi: 10.3892/mmr.2017.6771pubmed: 28627596google scholar: lookup
          19. Zhang Z, Leong DJ, Xu L, He Z, Wang A, Navati M, Kim SJ, Hirsh DM, Hardin JA, Cobelli NJ, Friedman JM, Sun HB. Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model.. Arthritis Res Ther 2016 Jun 3;18(1):128.
            doi: 10.1186/s13075-016-1025-ypubmed: 27260322google scholar: lookup
          20. Veronesi F, Fini M, Giavaresi G, Ongaro A, De Mattei M, Pellati A, Setti S, Tschon M. Experimentally induced cartilage degeneration treated by pulsed electromagnetic field stimulation; an in vitro study on bovine cartilage.. BMC Musculoskelet Disord 2015 Oct 20;16:308.
            doi: 10.1186/s12891-015-0760-6pubmed: 26480822google scholar: lookup
          21. Natarajan V, Madhan B, Tiku ML. Intra-Articular Injections of Polyphenols Protect Articular Cartilage from Inflammation-Induced Degradation: Suggesting a Potential Role in Cartilage Therapeutics.. PLoS One 2015;10(6):e0127165.
            doi: 10.1371/journal.pone.0127165pubmed: 26046639google scholar: lookup
          22. Hozhabri NS, Benson MD, Vu MD, Patel RH, Martinez RM, Nakhaie FN, Kim HK, Varanasi VG. Decreasing NF-u03baB expression enhances odontoblastic differentiation and collagen expression in dental pulp stem cells exposed to inflammatory cytokines.. PLoS One 2015;10(1):e0113334.
            doi: 10.1371/journal.pone.0113334pubmed: 25629155google scholar: lookup
          23. Zhao R, Peng X, Li Q, Song W. Effects of phosphorylatable short peptide-conjugated chitosan-mediated IL-1Ra and igf-1 gene transfer on articular cartilage defects in rabbits.. PLoS One 2014;9(11):e112284.
            doi: 10.1371/journal.pone.0112284pubmed: 25390659google scholar: lookup
          24. Appelboom T, Maes N, Albert A. A new curcuma extract (flexofytolu00ae) in osteoarthritis: results from a belgian real-life experience.. Open Rheumatol J 2014;8:77-81.
            doi: 10.2174/1874312901408010077pubmed: 25352926google scholar: lookup
          25. Leong DJ, Choudhury M, Hirsh DM, Hardin JA, Cobelli NJ, Sun HB. Nutraceuticals: potential for chondroprotection and molecular targeting of osteoarthritis.. Int J Mol Sci 2013 Nov 21;14(11):23063-85.
            doi: 10.3390/ijms141123063pubmed: 24284399google scholar: lookup
          26. Henrotin Y, Priem F, Mobasheri A. Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management.. Springerplus 2013 Dec;2(1):56.
            doi: 10.1186/2193-1801-2-56pubmed: 23487030google scholar: lookup
          27. Jabaut J, Ather JL, Taracanova A, Poynter ME, Ckless K. Mitochondria-targeted drugs enhance Nlrp3 inflammasome-dependent IL-1u03b2 secretion in association with alterations in cellular redox and energy status.. Free Radic Biol Med 2013 Jul;60:233-45.
          28. Mobasheri A. Intersection of inflammation and herbal medicine in the treatment of osteoarthritis.. Curr Rheumatol Rep 2012 Dec;14(6):604-16.
            doi: 10.1007/s11926-012-0288-9pubmed: 22987043google scholar: lookup
          29. Ather JL, Ckless K, Martin R, Foley KL, Suratt BT, Boyson JE, Fitzgerald KA, Flavell RA, Eisenbarth SC, Poynter ME. Serum amyloid A activates the NLRP3 inflammasome and promotes Th17 allergic asthma in mice.. J Immunol 2011 Jul 1;187(1):64-73.
            doi: 10.4049/jimmunol.1100500pubmed: 21622869google scholar: lookup
          30. Shakibaei M, Mobasheri A, Buhrmann C. Curcumin synergizes with resveratrol to stimulate the MAPK signaling pathway in human articular chondrocytes in vitro.. Genes Nutr 2011 May;6(2):171-9.
            doi: 10.1007/s12263-010-0179-5pubmed: 21484156google scholar: lookup
          31. Clutterbuck AL, Smith JR, Allaway D, Harris P, Liddell S, Mobasheri A. High throughput proteomic analysis of the secretome in an explant model of articular cartilage inflammation.. J Proteomics 2011 May 1;74(5):704-15.
            doi: 10.1016/j.jprot.2011.02.017pubmed: 21354348google scholar: lookup
          32. Wann AK, Mistry J, Blain EJ, Michael-Titus AT, Knight MM. Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1u03b2-mediated cartilage degradation.. Arthritis Res Ther 2010;12(6):R207.
            doi: 10.1186/ar3183pubmed: 21059244google scholar: lookup