Antioxidants and Osteoarthritis

  • Ali MobasheriEmail author
  • Hans Konrad Biesalski
  • Mehdi Shakibaei
  • Yves Henrotin
Reference work entry


Oxidative stress produces reactive oxygen species (ROS) that play key roles in the development of osteoarthritis (OA) and rheumatoid arthritis (RA). Metabolic reactions in chondrocytes and synoviocytes produce free radicals, ROS, and their derivatives. These dangerous chemicals can accumulate in the synovial joint, causing extensive structural damage, inflammation, and cell death. Antioxidants are naturally occurring reducing agents capable of inhibiting ROS formation, scavenging free radicals, and removing ROS derivatives. Antioxidant vitamins have major roles in modulating oxidative stress, regulating immune responses, and contributing to cell differentiation. Vitamin C (ascorbic acid), vitamin E, thiols (glutathione), and plant polyphenols have the capacity to neutralize ROS in joints and decrease the oxidative stress associated with the progression of arthritis. There is a pressing need to understand the contribution of antioxidants to OA, because they may provide important insight into ameliorating the initiation and progression of the disease. The objective of this chapter is to examine ROS biology at the cellular and tissue levels in the synovial joint with special emphasis on the biological effects of ROS and naturally occurring antioxidants on chondrocytes. We summarize and critically appraise the information published about antioxidants and their potential for preventing and treating arthritic diseases such as OA. The expectation is to relate the potential importance of dietary antioxidants and their supplementation in OA patients. This knowledge will improve the design of future clinical trials and interventional studies on OA and related diseases.


Antioxidant Cartilage Combination products Glutathione Inflammation Osteoarthritis Supplements Synovium Vitamin A Vitamin C Vitamin E 



A. Mobasheri wishes to acknowledge the generous financial support of the Wellcome Trust, the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) (grant number: Mobasheri.A.28102007), the Biotechnology and Biological Sciences Research Council (BBSRC) (grants BBSRC/S/M/2006/13141 and BB/G018030/1), and the Engineering and Physical Sciences Research Council (EPSRC).

Conflict of Interest Statement

This chapter was written by the authors within the scope of their academic and research positions at their host institutions. None of the authors has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of this chapter.


  1. Abramson SB (2008) Osteoarthritis and nitric oxide. Osteoarthr Cartil 16(Suppl 2):S15–S20PubMedGoogle Scholar
  2. Abramson SB, Attur M (2009) Developments in the scientific understanding of osteoarthritis. Arthritis Res Ther 11:227PubMedCentralPubMedGoogle Scholar
  3. Afonso V, Champy R, Mitrovic D, Collin P, Lomri A (2007) Reactive oxygen species and superoxide dismutases: role in joint diseases. Joint Bone Spine 74:324–329PubMedGoogle Scholar
  4. Aigner T, Rose J, Martin J, Buckwalter J (2004) Aging theories of primary osteoarthritis: from epidemiology to molecular biology. Rejuvenation Res 7:134–145PubMedGoogle Scholar
  5. Airley RE, Mobasheri A (2007) Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics. Chemotherapy 53:233–256PubMedGoogle Scholar
  6. Amin AR, Abramson SB (1998) The role of nitric oxide in articular cartilage breakdown in osteoarthritis. Curr Opin Rheumatol 10:263–268PubMedGoogle Scholar
  7. Archer CW, Francis-West P (2003) The chondrocyte. Int J Biochem Cell Biol 35:401–404PubMedGoogle Scholar
  8. Astuya A, Caprile T, Castro M, Salazar K, Garcia Mde L, Reinicke K, Rodriguez F, Vera JC, Millan C, Ulloa V, Low M, Martinez F, Nualart F (2005) Vitamin C uptake and recycling among normal and tumor cells from the central nervous system. J Neurosci Res 79:146–156PubMedGoogle Scholar
  9. Baker MS, Feigan J, Lowther DA (1988) Chondrocyte antioxidant defences: the roles of catalase and glutathione peroxidase in protection against H2O2 dependent inhibition of proteoglycan biosynthesis. J Rheumatol 15:670–677PubMedGoogle Scholar
  10. Besse JL, Gadeyne S, Galand-Desme S, Lerat JL, Moyen B (2009) Effect of vitamin C on prevention of complex regional pain syndrome type I in foot and ankle surgery. Foot Ankle Surg 15:179–182PubMedGoogle Scholar
  11. Biesalski HK (2008) Parenteral ascorbic acid as a key for regulating microcirculation in critically ill. Crit Care Med 36:2466–2468PubMedGoogle Scholar
  12. Biesalski HK, Brummer RJ, Konig J, O’Connell MA, Ovesen L, Rechkemmer G, Stos K, Thurnham DI (2003) Micronutrient deficiencies. Hohenheim consensus conference. Eur J Nutr 42:353–363PubMedGoogle Scholar
  13. Biesalski HK, Tinz J (2008) Nutritargeting. Adv Food Nutr Res 54:179–217PubMedGoogle Scholar
  14. Blanco FJ, Lopez-Armada MJ, Maneiro E (2004) Mitochondrial dysfunction in osteoarthritis. Mitochondrion 4:715–728PubMedGoogle Scholar
  15. Blanco FJ, Rego I, Ruiz-Romero C (2011) The role of mitochondria in osteoarthritis. Nat Rev Rheumatol 7:161–169PubMedGoogle Scholar
  16. Brand C, Snaddon J, Bailey M, Cicuttini F (2001) Vitamin E is ineffective for symptomatic relief of knee osteoarthritis: a six month double blind, randomised, placebo controlled study. Ann Rheum Dis 60:946–949PubMedCentralPubMedGoogle Scholar
  17. Buckwalter JA, Mankin HJ, Grodzinsky AJ (2005) Articular cartilage and osteoarthritis. Instr Course Lect 54:465–480PubMedGoogle Scholar
  18. Calabrese EJ (2005) Cancer biology and hormesis: human tumor cell lines commonly display hormetic (biphasic) dose responses. Crit Rev Toxicol 35:463–582PubMedGoogle Scholar
  19. Calabrese EJ, Blain R (2005) The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview. Toxicol Appl Pharmacol 202:289–301PubMedGoogle Scholar
  20. Canter PH, Wider B, Ernst E (2007) The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a systematic review of randomized clinical trials. Rheumatology (Oxford) 46:1223–1233Google Scholar
  21. Carames B, Taniguchi N, Otsuki S, Blanco FJ, Lotz M (2010) Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis. Arthritis Rheum 62:791–801PubMedCentralPubMedGoogle Scholar
  22. Carlo MD Jr, Loeser RF (2003) Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum 48:3419–3430PubMedGoogle Scholar
  23. Castro MA, Angulo C, Brauchi S, Nualart F, Concha II (2008) Ascorbic acid participates in a general mechanism for concerted glucose transport inhibition and lactate transport stimulation. Pflugers Arch 457:519–528PubMedGoogle Scholar
  24. Chakravarthi S, Jessop CE, Bulleid NJ (2006) The role of glutathione in disulphide bond formation and endoplasmic-reticulum-generated oxidative stress. EMBO Rep 7:271–275PubMedCentralPubMedGoogle Scholar
  25. Corthesy-Theulaz I, den Dunnen JT, Ferre P, Geurts JM, Muller M, van Belzen N, van Ommen B (2005) Nutrigenomics: the impact of biomics technology on nutrition research. Ann Nutr Metab 49:355–365PubMedGoogle Scholar
  26. Deahl ST 2nd, Oberley LW, Oberley TD, Elwell JH (1992) Immunohistochemical identification of superoxide dismutases, catalase, and glutathione-S-transferases in rat femora. J Bone Miner Res 7:187–198PubMedGoogle Scholar
  27. Di Paola R, Cuzzocrea S (2008) Predictivity and sensitivity of animal models of arthritis. Autoimmun Rev 8:73–75PubMedGoogle Scholar
  28. Englard S, Seifter S (1986) The biochemical functions of ascorbic acid. Annu Rev Nutr 6:365–406PubMedGoogle Scholar
  29. Feelisch M (2008) The chemical biology of nitric oxide – an outsider’s reflections about its role in osteoarthritis. Osteoarthr Cartil 16(Suppl 2):S3–S13PubMedGoogle Scholar
  30. Findlay DM (2007) Vascular pathology and osteoarthritis. Rheumatology (Oxford) 46:1763–1768Google Scholar
  31. Fragonas E, Pollesello P, Mlinarik V, Toffanin R, Grando C, Godeas C, Vittur F (1998) Sensitivity of chondrocytes of growing cartilage to reactive oxygen species. Biochim Biophys Acta 1425:103–111PubMedGoogle Scholar
  32. Gabay O, Hall DJ, Berenbaum F, Henrotin Y, Sanchez C (2008) Osteoarthritis and obesity: experimental models. Joint Bone Spine 75:675–679PubMedCentralPubMedGoogle Scholar
  33. Gerster H (1997) Vitamin A – functions, dietary requirements and safety in humans. Int J Vitam Nutr Res 67:71–90PubMedGoogle Scholar
  34. Gloire G, Legrand-Poels S, Piette J (2006) NF-kappaB activation by reactive oxygen species: fifteen years later. Biochem Pharmacol 72:1493–1505PubMedGoogle Scholar
  35. Goggs R, Carter SD, Schulze-Tanzil G, Shakibaei M, Mobasheri A (2003) Apoptosis and the loss of chondrocyte survival signals contribute to articular cartilage degradation in osteoarthritis. Vet J 166:140–158PubMedGoogle Scholar
  36. Goldring MB, Goldring SR (2007) Osteoarthritis. J Cell Physiol 213:626–634PubMedGoogle Scholar
  37. Griffin TM, Guilak F (2008) Why is obesity associated with osteoarthritis? Insights from mouse models of obesity. Biorheology 45:387–398PubMedCentralPubMedGoogle Scholar
  38. He SJ, Hou JF, Dai YY, Zhou ZL, Deng YF (2011) N-acetyl-cysteine protects chicken growth plate chondrocytes from T-2 toxin-induced oxidative stress. J Appl Toxicol 32(12):980–985PubMedGoogle Scholar
  39. Henrotin Y, Kurz B (2007) Antioxidant to treat osteoarthritis: dream or reality? Curr Drug Targets 8:347–357PubMedGoogle Scholar
  40. Henrotin Y, Deby-Dupont G, Deby C, Franchimont P, Emerit I (1992) Active oxygen species, articular inflammation and cartilage damage. EXS 62:308–322PubMedGoogle Scholar
  41. Henrotin YE, Bruckner P, Pujol JP (2003) The role of reactive oxygen species in homeostasis and degradation of cartilage. Osteoarthr Cartil 11:747–755PubMedGoogle Scholar
  42. Henrotin Y, Clutterbuck AL, Allaway D, Lodwig EM, Harris P, Mathy-Hartert M, Shakibaei M, Mobasheri A (2010) Biological actions of curcumin on articular chondrocytes. Osteoarthr Cartil 18:141–149PubMedGoogle Scholar
  43. Hinds TS, West WL, Knight EM (1997) Carotenoids and retinoids: a review of research, clinical, and public health applications. J Clin Pharmacol 37:551–558PubMedGoogle Scholar
  44. Hiran TS, Moulton PJ, Hancock JT (1997) Detection of superoxide and NADPH oxidase in porcine articular chondrocytes. Free Radic Biol Med 23:736–743PubMedGoogle Scholar
  45. Hiran TS, Moulton PJ, Hancock JT (1998) In situ detection of superoxide anions within porcine articular cartilage. Br J Biomed Sci 55:199–203PubMedGoogle Scholar
  46. Iannone F, Lapadula G (2010) Obesity and inflammation – targets for OA therapy. Curr Drug Targets 11:586–598PubMedGoogle Scholar
  47. Imhof H, Sulzbacher I, Grampp S, Czerny C, Youssefzadeh S, Kainberger F (2000) Subchondral bone and cartilage disease: a rediscovered functional unit. Invest Radiol 35:581–588PubMedGoogle Scholar
  48. Jaiman A, Lokesh M, Neogi DS (2011) Effect of vitamin C on prevention of complex regional pain syndrome type I in foot and ankle surgery. Foot Ankle Surg 17:207PubMedGoogle Scholar
  49. Jaswal S, Mehta HC, Sood AK, Kaur J (2003) Antioxidant status in rheumatoid arthritis and role of antioxidant therapy. Clin Chim Acta 338:123–129PubMedGoogle Scholar
  50. Jha P, Flather M, Lonn E, Farkouh M, Yusuf S (1995) The antioxidant vitamins and cardiovascular disease. A critical review of epidemiologic and clinical trial data. Ann Intern Med 123:860–872PubMedGoogle Scholar
  51. Kapoor S (2012) Vitamin C and its emerging role in pain management: beneficial effects in pain conditions besides post herpetic neuralgia. Korean J Pain 25:200–201PubMedCentralPubMedGoogle Scholar
  52. Konstantinidou V, Covas MI, Munoz-Aguayo D, Khymenets O, de la Torre R, Saez G, Tormos Mdel C, Toledo E, Marti A, Ruiz-Gutierrez V, Ruiz Mendez MV, Fito M (2010) In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial. FASEB J 24:2546–2557PubMedGoogle Scholar
  53. Lafont JE (2010) Lack of oxygen in articular cartilage: consequences for chondrocyte biology. Int J Exp Pathol 91:99–106PubMedCentralPubMedGoogle Scholar
  54. Levick JR (1995) Microvascular architecture and exchange in synovial joints. Microcirculation 2:217–233PubMedGoogle Scholar
  55. Li WQ, Dehnade F, Zafarullah M (2000) Thiol antioxidant, N-acetylcysteine, activates extracellular signal-regulated kinase signaling pathway in articular chondrocytes. Biochem Biophys Res Commun 275:789–794PubMedGoogle Scholar
  56. Loeser RF (2011) Aging and osteoarthritis. Curr Opin Rheumatol 23:492–496PubMedCentralPubMedGoogle Scholar
  57. Lotz MK, Kraus VB (2010) New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options. Arthritis Res Ther 12:211PubMedCentralPubMedGoogle Scholar
  58. Machlin LJ, Bendich A (1987) Free radical tissue damage: protective role of antioxidant nutrients. FASEB J 1:441–445PubMedGoogle Scholar
  59. May JM (1998) Ascorbate function and metabolism in the human erythrocyte. Front Biosci 3:d1–d10PubMedGoogle Scholar
  60. McAlindon TE, Jacques P, Zhang Y, Hannan MT, Aliabadi P, Weissman B, Rush D, Levy D, Felson DT (1996) Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis? Arthritis Rheum 39:648–656PubMedGoogle Scholar
  61. McGregor GP, Biesalski HK (2006) Rationale and impact of vitamin C in clinical nutrition. Curr Opin Clin Nutr Metab Care 9:697–703PubMedGoogle Scholar
  62. McNulty AL, Stabler TV, Vail TP, McDaniel GE, Kraus VB (2005a) Dehydroascorbate transport in human chondrocytes is regulated by hypoxia and is a physiologically relevant source of ascorbic acid in the joint. Arthritis Rheum 52:2676–2685PubMedGoogle Scholar
  63. McNulty AL, Vail TP, Kraus VB (2005b) Chondrocyte transport and concentration of ascorbic acid is mediated by SVCT2. Biochim Biophys Acta 1712:212–221PubMedGoogle Scholar
  64. Meister A (1994a) Glutathione-ascorbic acid antioxidant system in animals. J Biol Chem 269:9397–9400PubMedGoogle Scholar
  65. Meister A (1994b) Glutathione, ascorbate, and cellular protection. Cancer Res 54:1969s–1975sPubMedGoogle Scholar
  66. Michiels C, Raes M, Zachary MD, Delaive E, Remacle J (1988) Microinjection of antibodies against superoxide dismutase and glutathione peroxidase. Exp Cell Res 179:581–589PubMedGoogle Scholar
  67. Mobasheri A (2002) Role of chondrocyte death and hypocellularity in ageing human articular cartilage and the pathogenesis of osteoarthritis. Med Hypotheses 58:193–197PubMedGoogle Scholar
  68. Mobasheri A, Vannucci SJ, Bondy CA, Carter SD, Innes JF, Arteaga MF, Trujillo E, Ferraz I, Shakibaei M, Martin-Vasallo P (2002) Glucose transport and metabolism in chondrocytes: a key to understanding chondrogenesis, skeletal development and cartilage degradation in osteoarthritis. Histol Histopathol 17:1239–1267PubMedGoogle Scholar
  69. Mobasheri A, Bondy CA, Moley K, Mendes AF, Rosa SC, Richardson SM, Hoyland JA, Barrett-Jolley R, Shakibaei M (2008) Facilitative glucose transporters in articular chondrocytes. Expression, distribution and functional regulation of GLUT isoforms by hypoxia, hypoxia mimetics, growth factors and pro-inflammatory cytokines. Adv Anat Embryol Cell Biol 200(1):1–84PubMedGoogle Scholar
  70. Montel-Hagen A, Sitbon M, Taylor N (2009) Erythroid glucose transporters. Curr Opin Hematol 16:165–172PubMedGoogle Scholar
  71. Moulton PJ, Hiran TS, Goldring MB, Hancock JT (1997) Detection of protein and mRNA of various components of the NADPH oxidase complex in an immortalized human chondrocyte line. Br J Rheumatol 36:522–529PubMedGoogle Scholar
  72. Moulton PJ, Goldring MB, Hancock JT (1998) NADPH oxidase of chondrocytes contains an isoform of the gp91phox subunit. Biochem J 329(Pt 3):449–451PubMedCentralPubMedGoogle Scholar
  73. Muhlhofer A, Mrosek S, Schlegel B, Trommer W, Rozario F, Bohles H, Schremmer D, Zoller WG, Biesalski HK (2004) High-dose intravenous vitamin C is not associated with an increase of pro-oxidative biomarkers. Eur J Clin Nutr 58:1151–1158PubMedGoogle Scholar
  74. Nakagawa S, Arai Y, Mazda O, Kishida T, Takahashi KA, Sakao K, Saito M, Honjo K, Imanishi J, Kubo T (2010) N-acetylcysteine prevents nitric oxide-induced chondrocyte apoptosis and cartilage degeneration in an experimental model of osteoarthritis. J Orthop Res 28:156–163PubMedGoogle Scholar
  75. Ogura Y, Sutterwala FS, Flavell RA (2006) The inflammasome: first line of the immune response to cell stress. Cell 126:659–662PubMedGoogle Scholar
  76. Oliver JE, Silman AJ (2009) What epidemiology has told us about risk factors and aetiopathogenesis in rheumatic diseases. Arthritis Res Ther 11:223PubMedCentralPubMedGoogle Scholar
  77. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK, Levine M (2003) Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 22:18–35PubMedGoogle Scholar
  78. Parke DV, Sapota A (1996) Chemical toxicity and reactive oxygen species. Int J Occup Med Environ Health 9:331–340PubMedGoogle Scholar
  79. Peregoy J, Wilder FV (2011) The effects of vitamin C supplementation on incident and progressive knee osteoarthritis: a longitudinal study. Public Health Nutr 14:709–715PubMedGoogle Scholar
  80. Pfander D, Gelse K (2007) Hypoxia and osteoarthritis: how chondrocytes survive hypoxic environments. Curr Opin Rheumatol 19:457–462PubMedGoogle Scholar
  81. Rahman I, Biswas SK, Kirkham PA (2006) Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol 72:1439–1452PubMedGoogle Scholar
  82. Rattan SI (2008) Hormesis in aging. Ageing Res Rev 7:63–78PubMedGoogle Scholar
  83. Rattan SI, Ali RE (2007) Hormetic prevention of molecular damage during cellular aging of human skin fibroblasts and keratinocytes. Ann N Y Acad Sci 1100:424–430PubMedGoogle Scholar
  84. Ristow M, Schmeisser S (2011) Extending life span by increasing oxidative stress. Free Radic Biol Med 51:327–336PubMedGoogle Scholar
  85. Rosenbaum CC, O’Mathuna DP, Chavez M, Shields K (2010) Antioxidants and antiinflammatory dietary supplements for osteoarthritis and rheumatoid arthritis. Altern Ther Health Med 16:32–40PubMedGoogle Scholar
  86. Ross AC, Gardner EM (1994) The function of vitamin A in cellular growth and differentiation, and its roles during pregnancy and lactation. Adv Exp Med Biol 352:187–200PubMedGoogle Scholar
  87. Schreck R, Rieber P, Baeuerle PA (1991) Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J 10:2247–2258PubMedCentralPubMedGoogle Scholar
  88. Sellam J, Berenbaum F (2010) The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol 6:625–635PubMedGoogle Scholar
  89. Semba RD (1998) The role of vitamin A and related retinoids in immune function. Nutr Rev 56:S38–S48PubMedGoogle Scholar
  90. Siegel GJ, Agranoff BW, Albers RW et al. (eds) (1999) Basic neurochemistry: molecular, cellularand medical aspects, 6th edn. Lippincott-Raven, Philadelphia.Google Scholar
  91. Sowers M, Lachance L (1999) Vitamins and arthritis. The roles of vitamins A, C, D, and E. Rheum Dis Clin North Am 25:315–332PubMedGoogle Scholar
  92. Stucki G, Liang MH, Stucki S, Bruhlmann P, Michel BA (1995) A self-administered rheumatoid arthritis disease activity index (RADAI) for epidemiologic research. Psychometric properties and correlation with parameters of disease activity. Arthritis Rheum 38:795–798PubMedGoogle Scholar
  93. Studer RK (2004) Nitric oxide decreases IGF-1 receptor function in vitro; glutathione depletion enhances this effect in vivo. Osteoarthr Cartil 12:863–869PubMedGoogle Scholar
  94. Sutton S, Clutterbuck A, Harris P, Gent T, Freeman S, Foster N, Barrett-Jolley R, Mobasheri A (2009) The contribution of the synovium, synovial derived inflammatory cytokines and neuropeptides to the pathogenesis of osteoarthritis. Vet J 179:10–24PubMedGoogle Scholar
  95. Terkeltaub R, Johnson K, Murphy A, Ghosh S (2002) Invited review: the mitochondrion in osteoarthritis. Mitochondrion 1:301–319PubMedGoogle Scholar
  96. Troadec MB, Kaplan J (2008) Some vertebrates go with the GLO. Cell 132:921–922PubMedGoogle Scholar
  97. Tschopp J (2011) Mitochondria: sovereign of inflammation? Eur J Immunol 41:1196–1202PubMedGoogle Scholar
  98. Ueno T, Yamada M, Sugita Y, Ogawa T (2011) N-acetyl cysteine protects TMJ chondrocytes from oxidative stress. J Dent Res 90:353–359PubMedGoogle Scholar
  99. Vaillancourt F, Fahmi H, Shi Q, Lavigne P, Ranger P, Fernandes JC, Benderdour M (2008) 4-Hydroxynonenal induces apoptosis in human osteoarthritic chondrocytes: the protective role of glutathione-S-transferase. Arthritis Res Ther 10:R107PubMedCentralPubMedGoogle Scholar
  100. van Ommen B (2004) Nutrigenomics: exploiting systems biology in the nutrition and health arenas. Nutrition 20:4–8PubMedGoogle Scholar
  101. van Ommen B (2007) Personalized nutrition from a health perspective: luxury or necessity? Genes Nutr 2:3–4PubMedCentralPubMedGoogle Scholar
  102. van Ommen B, Stierum R (2002) Nutrigenomics: exploiting systems biology in the nutrition and health arena. Curr Opin Biotechnol 13:517–521PubMedGoogle Scholar
  103. van Ommen B, Keijer J, Heil SG, Kaput J (2009) Challenging homeostasis to define biomarkers for nutrition related health. Mol Nutr Food Res 53:795–804PubMedGoogle Scholar
  104. Wang Y, Hodge AM, Wluka AE, English DR, Giles GG, O’Sullivan R, Forbes A, Cicuttini FM (2007) Effect of antioxidants on knee cartilage and bone in healthy, middle-aged subjects: a cross-sectional study. Arthritis Res Ther 9:R66PubMedCentralPubMedGoogle Scholar
  105. Wiseman H (1993) Vitamin D is a membrane antioxidant. Ability to inhibit iron-dependent lipid peroxidation in liposomes compared to cholesterol, ergosterol and tamoxifen and relevance to anticancer action. FEBS Lett 326:285–288PubMedGoogle Scholar
  106. Wluka AE, Stuckey S, Brand C, Cicuttini FM (2002) Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a 2 year double blind randomized placebo controlled study. J Rheumatol 29:2585–2591PubMedGoogle Scholar
  107. Wolf G (1996) The mechanism of uptake of ascorbic acid into osteoblasts and leukocytes. Nutr Rev 54:150–152PubMedGoogle Scholar
  108. Woolf AD, Pfleger B (2003) Burden of major musculoskeletal conditions. Bull World Health Organ 81:646–656PubMedCentralPubMedGoogle Scholar
  109. Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469:221–225PubMedGoogle Scholar
  110. Ziskoven C, Jager M, Kircher J, Patzer T, Bloch W, Brixius K, Krauspe R (2011) Physiology and pathophysiology of nitrosative and oxidative stress in osteoarthritic joint destruction. Can J Physiol Pharmacol 89:455–466PubMedGoogle Scholar
  111. Zollinger PE, Ellis ML, Unal H, Tuinebreijer WE (2008) Clinical outcome of cementless semi-constrained trapeziometacarpal arthroplasty, and possible effect of vitamin C on the occurrence of complex regional pain syndrome. Acta Orthop Belg 74:317–322PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ali Mobasheri
    • 1
    • 2
    Email author
  • Hans Konrad Biesalski
    • 3
  • Mehdi Shakibaei
    • 4
  • Yves Henrotin
    • 5
  1. 1.Arthritis Research UK Centres for Pain, Musculoskeletal Ageing Research and Sport, Exercise and Osteoarthritis, Faculty of Medicine and Health SciencesThe University of NottinghamLeicestershireUK
  2. 2.Center of Excellence in Genomic Medicine Research (CEGMR), King Fahad Medical Research CenterKing Abdulaziz UniversityJeddahKingdom of Saudi Arabia
  3. 3.Department of Biological Chemistry and Nutrition, Institute of Biological Chemistry and NutritionUniversity of HohenheimStuttgartGermany
  4. 4.Musculoskeletal Research Group, Institute of AnatomyLudwig-Maximilian-University MunichMunichGermany
  5. 5.Bone and Cartilage Research Unit, Institute of PathologyUniversity of LiègeLiègeBelgium

Personalised recommendations