Rheumatology International

, Volume 32, Issue 6, pp 1541–1548 | Cite as

Effect of resveratrol on cartilage protection and apoptosis inhibition in experimental osteoarthritis of rabbit

  • Jing Wang
  • Jie-Sheng GaoEmail author
  • Jin-Wei Chen
  • Fen Li
  • Jing Tian
Original Article


To observe the effect of resveratol on cartilage,chondrocyte apoptosis, and nitric oxide in experimental osteoarthritis (OA) of rabbit and to study the mechanism of resveratol in the treatment of osteoarthritis. Thirty New Zealand rabbits were randomly divided into 5 groups: group A (normal control group), group B (model control group), group C (resveratrol intervention high-dosage group), group D (resveratrol intervention middle dosage group), and group E (resveratrol intervention low-dosage group). The model of OA of the knee was established using Hulth technique in groups B, C, D, and E. After 4 weeks, group A and group B rabbits were administered daily a knees injection of dimethylsulfoxide (DMSO), whereas groups C, D, and E were administered daily a knees injection of resveratrol in DMSO in different dosages for 2 weeks. Daily dosage for rabbits of groups C, D, and E was fixed at 50, 20, and 10 μmol/kg, respectively. Then, the rabbits were killed, and the lateral cartilage sections of right femoral medial condyle were evaluated using a histological scoring system (H&E and safranin-O staining) and analyzed by TUNEL for apoptosis. Nitric oxide (NO) in synovial fluid was measured by nitrate reduction method. Histological evaluation of cartilage tissue revealed a significantly reduced cartilage destruction; the evaluation also revealed the loss of matrix proteoglycan content in cartilage in resveratrol intervention groups compared to the model control. Resveratrol reduced the apoptosis rate of chondrocyte and level of NO in the synovial fluid. In the above experiments of OA rabbits, the protective effects of resveratrol were enhanced with increased resveratrol dosage. Resveratrol controls the progression of experimental OA. One of the mechanism(s) responsible for this effect would include lowering of the apoptosis rate of chondrocyte and reducing the production of NO in experimental OA.


Resveratrol Cartilage Osteoarthritis Apoptosis Chondrocyte 


  1. 1.
    Hashimoto S, Ochs RL, Komiya S et al (1998) Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis. Arthritis Rheum 41(9):1632–1638PubMedCrossRefGoogle Scholar
  2. 2.
    Chen MH, Wang JL, Wong CY et al (2005) Relationship of chondrocyte apoptosis to matrix degradation and swelling potential of osteoarthritic cartilage. J Formos Med Assoc 104(4):264–272PubMedGoogle Scholar
  3. 3.
    Hashimoto S, Setareh M, Ochs RL et al (1997) Fas/Fas ligand expression and induction of apoptosis in chondrocytes. Arthritis Rheum 40(10):1749–1755PubMedCrossRefGoogle Scholar
  4. 4.
    López-Armada M, Caramés B, Lires-Deán M et al (2006) Cytokines, tumor necrosis factor-α and interleukin-1β, differentially regulate apoptosis in osteoarthritis cultured human chondrocytes. Osteoarthr Cartil 14(7):660–669PubMedCrossRefGoogle Scholar
  5. 5.
    Abramson SB (2008) Osteoarthritis and nitric oxide. Osteoarthr Cartil 16(Suppl 2):S15–S20PubMedCrossRefGoogle Scholar
  6. 6.
    de la Lastra CA, Villegas I (2005) Resveratrol as an anti-inflammatory and anti-aging agent: Mechanisms and clinical implications. Mol Nutr Food Res 49(5):405–430CrossRefGoogle Scholar
  7. 7.
    Udenigwe CC, Ramprasath VR, Aluko RE et al (2008) Potential of resveratrol in anticancer and anti-inflammatory therapy. Nutr Rev 66(8):445–454PubMedCrossRefGoogle Scholar
  8. 8.
    Manna SK, Mukhopadhyay A, Aggarwal BB (2000) Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappaB, activator protein-1 and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol 164(12):6509–6519PubMedGoogle Scholar
  9. 9.
    Holmes-McNary M, Baldwin AS Jr (2000) Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase. Cancer Res 60(13):3477–3483PubMedGoogle Scholar
  10. 10.
    Surh YJ, Chun KS, Cha HH et al (2001) Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res 1(480–481):243–268Google Scholar
  11. 11.
    Estrov Z, Shishodia S, Faderl S et al (2003) Resveratrol blocks interleukin-1beta-induced activation of the nuclear transcription factor NF-kappaB, inhibits proliferation, causes S-phase arrest, and induces apoptosis of acute myeloid leukemia cells. Blood 102(3):987–995PubMedCrossRefGoogle Scholar
  12. 12.
    Kuhn K, Hashimoto S, Lotz M (2000) IL-1 beta protects human chondrocytes from CD95-induced apoptosis. J Immunol 164(4):2233–2239PubMedGoogle Scholar
  13. 13.
    Kim SJ, Chun JS (2003) Protein kinase C alpha and zeta regulate nitric oxide-induced NF-kappa B activation that mediates cyclooxygenase-2 expression and apoptosis but not dedifferentiation in articular chondrocytes. Biochem Biophys Res Commun 303(1):206–211PubMedCrossRefGoogle Scholar
  14. 14.
    Mendes AF, Carvalho AP, Caramona MM et al (2002) Role of nitric oxide in the activation of NF-kappaB, AP-1 and NOS II expression in articular chondrocytes. Inflamm Res 51(7):369–375PubMedCrossRefGoogle Scholar
  15. 15.
    Martel-Pelletier J, Mineau F, Jovanovic D et al (1999) Mitogen-activated protein kinase and nuclear factor kappaB together regulate interleukin-17-induced nitric oxide production in human osteoarthritic chondrocytes: possible role of transactivating factor mitogen-activated protein kinase-activated protein kinase (MAPKAPK). Arthritis Rheum 42(11):2399–2409PubMedCrossRefGoogle Scholar
  16. 16.
    Shalom-Barak T, Quach J, Lotz M (1998) Interleukin-17-induced gene expression in articular chondrocytes is associated with activation of mitogen-activated protein kinases and NF-kappaB. J Biol Chem 273(42):27467–27473PubMedCrossRefGoogle Scholar
  17. 17.
    Shakibaei M, John T, Seifarth C et al (2007) Resveratrol inhibits IL-1beta-induced stimulation of caspase-3 and cleavage of PARP in human articular chondrocytes in vitro. Ann N Y Acad Sci 1095(1):554–563PubMedCrossRefGoogle Scholar
  18. 18.
    Dave M, Attur M, Palmer G et al (2008) The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production. Arthritis Rheum 58(9):2786–2797PubMedCrossRefGoogle Scholar
  19. 19.
    Elmali N, Esenkaya I, Harma A et al (2005) Effect of resveratrol in experimental osteoarthritis in rabbits. Inflamm Res 54(4):158–162PubMedCrossRefGoogle Scholar
  20. 20.
    Blanco FJ, Guitian R, Vazquez-Martul E et al (1998) Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology. Arthritis Rheum 41(2):284–289PubMedCrossRefGoogle Scholar
  21. 21.
    D’Lima D, Hermida J, Hashimoto S et al (2006) Caspase inhibitors reduce severity of cartilage lesions in experimental osteoarthritis. Arthritis Rheum 54(6):1814–1821PubMedCrossRefGoogle Scholar
  22. 22.
    Pelletier JP, Jovanovic DV, Lascau Coman V et al (2000) Selective inhibitor of inducible nitric oxide synthase reduces progression of experimental osteoarthritis in vivo: possible link with the reduction in chondrocyte apoptosis and caspase–3 level. Arthritis Rheum 43(6):1290–1299PubMedCrossRefGoogle Scholar
  23. 23.
    Pelletier JP, Lascau-Coman V, Jovanovic D et al (1999) Selective inhibition of inducible nitric oxide synthase in experimental osteoarthritis is associated with reduction in tissue levels of catabolic factors. J Rheumatol 26(9):2002–2014PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Jing Wang
    • 1
  • Jie-Sheng Gao
    • 1
    Email author
  • Jin-Wei Chen
    • 1
  • Fen Li
    • 1
  • Jing Tian
    • 1
  1. 1.Department of RheumatologyThe Second Xiangya Hospital of Central-South UniversityChangshaChina

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