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Cell and Tissue Research

, Volume 319, Issue 3, pp 439–445 | Cite as

Estradiol protects cultured articular chondrocytes from oxygen-radical-induced damage

  • Horst Claassen
  • Michael Schünke
  • Bodo Kurz
Regular Article

Abstract

Osteoarthritis (OA) is aggravated in menopausal women possibly because of changed serum estrogen levels. Estradiol has been postulated to affect oxidative stress induced by reactive oxygen species (ROS) in articular chondrocytes. We generated ROS in cultured bovine articular chondrocytes by incubating them with combined Fe2SO4, vitamin C, and hydrogen peroxide. The release of thiobarbituric-acid-reactive substances (TBARS, lipid peroxidation) and lactate dehydrogenase (LDH, membrane damage) was measured photometrically. Various estradiol doses and vitamin E, serving as control with an established anti-oxidative capacity, were applied either upon each exchange of medium and during radical production (strategy 1) or only during radical production (strategy 2). In chondrocytes incubated according to strategy 1, the production of TBARS and LDH release were significantly suppressed by 10−10–10−4 M estradiol or by vitamin E. Under strategy 2, the production of TBARS was significantly suppressed at estradiol concentrations higher than 10−6 M, whereas LDH release was inhibited at concentrations of 10−6–10−4 M. Vitamin E showed no significant effects. As repeated application of estradiol and vitamin E produced the best results, estradiol, like vitamin E, was speculated to accumulate in the plasma membrane and to decrease membrane fluidity resulting in protection against lipid peroxidation (non-genomic effect). Thus, in contrast to the neuroprotective effect of 17β-estradiol in supraphysiological doses reported recently, the anti-oxidative potential of estradiol appears to protect articular chondrocytes from ROS-induced damage when the hormone is given repeatedly in a physiological range. Decreased estradiol levels may therefore contribute to menopausal OA in the long term.

Keywords

Articular cartilage Reactive oxygen species Anti-oxidants Menopause 17β-Estradiol Bovine 

Notes

Acknowledgements

We thank Rita Kirsch, Claudia Kremling, and Frank Lichte for their skillful assistance during the experiments.

References

  1. Arteaga E, Rojas A, Villaseca P, Bianchi M (2000) The effect of 17beta-estradiol and alpha-tocopherol on the oxidation of LDL cholesterol from postmenopausal women and the minor effect of gamma-tocopherol and melatonin. Menopause 7:112–116Google Scholar
  2. Arteaga E, Villaseca P, Bianchi M, Rojas A, Marshall G (2003) Raloxifene is a better antioxidant of low-density lipoprotein than estradiol or tamoxifen in postmenopausal women in vitro. Menopause 10:142–146CrossRefGoogle Scholar
  3. Ayres S, Tang M, Subbiah MT (1996) Estradiol-17beta as an antioxidant: some distinct features when compared with common fat-soluble antioxidants. J Lab Clin Med 128:367–375Google Scholar
  4. Bates EJ, Lowther DA, Handley CJ (1984) Oxygen free-radicals mediate an inhibition of proteoglycan synthesis in cultured articular cartilage. Ann Rheum Dis 43:462–469Google Scholar
  5. Bednarek-Tupikowska G, Bohdanowicz-Pawlak A, Bidzinska B, Milewicz A, Antonowicz-Juchniewicz J, Andrzejak R (2001) Serum lipid peroxide levels and erythrocyte glutathione peroxidase and superoxide dismutase activity in premenopausal and postmenopausal women. Gynecol Endocrinol 15:298–303Google Scholar
  6. Brigelius-Flohé R, Traber MG (1999) Vitamin E: function and metabolism. FASEB J 13:1145–1155Google Scholar
  7. Brigelius-Flohé R, Kelly FJ, Salonen JT, Neuzil J, Zingg JM, Azzi A (2002) The European perspective on vitamin E: current knowledge and future research. Am J Clin Nutr 76:703–716Google Scholar
  8. Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310Google Scholar
  9. Cadenas E (1989) Biochemistry of oxygen toxicity. Annu Rev Biochem 58:79–110CrossRefPubMedGoogle Scholar
  10. Cutollo M, Balleari E, Giusti M, Monachesi M, Accardo S (1986) Sex hormone status in women suffering from rheumatoid arthritis. J Rheumatol 13:1019–1023Google Scholar
  11. Dequeker J (1985) The relationship between osteoporosis and osteoarthritis. Clin Rheum Dis 11:271–296Google Scholar
  12. Dudenhausen JW, Schneider HPG, Bastert G (2003) Frauenheilkunde und Geburtshilfe, 2. Auflage, de Gruyter, Berlin New YorkGoogle Scholar
  13. Felson DT (1990) The epidemiology of knee osteoarthritis: results from the Framingham osteoarthritis study. Semin Arthritis Rheum 20:42–50CrossRefGoogle Scholar
  14. Ham KD, Loeser RF, Lindgren BR, Carlson CS (2002) Effects of long-term estrogen replacement therapy on osteoarthritis severity in cynomolgus monkeys. Arthritis Rheum 46:1956–1964CrossRefGoogle Scholar
  15. Heron P, Daya S (2000) 17Beta-estradiol protects against quinolinic acid-induced lipid peroxidation in the rat brain. Metab Brain Dis 15:267–274CrossRefGoogle Scholar
  16. Jain SK (1983) Vitamin E and stabilization of membrane lipid organization in red blood cells with peroxidative damage. Biomed Biochim Acta 43:43–47Google Scholar
  17. Karsten U, Wollenberger A (1977) Improvements in the ethidium bromide method for direct fluorometric estimation of DNA and RNA in cell and tissue homogenates. Anal Biochem 77:464–470CrossRefGoogle Scholar
  18. Kuhl H (2001) Natürliche und synthetische Steroidhormone. In: Diedrich K (ed) Klinik der Frauenheilkunde und Geburtshilfe, Bd. 1, Endokrinologie und Reproduktionsmedizin I. Urban & Fischer, München Jena, p 78Google Scholar
  19. Kurz B, Schünke M (1997) Articular chondrocytes and synoviocytes in culture: influence of antioxidants on lipid peroxidation and proliferation. Ann Anat 179:439–446Google Scholar
  20. Kurz B, Steinhagen J, Schünke M (1999) Articular chondrocytes and synoviocytes in a co-culture system: influence on reactive oxygen species-induced cytotoxicity and lipid peroxidation. Cell Tissue Res 296:555–563CrossRefGoogle Scholar
  21. Kurz B, Jost B, Schünke M (2002) Dietary vitamins and selenium diminish the development of mechanically induced osteoarthritis and increase the expression of antioxidative enzymes in the knee joint of STR/1N mice. Osteoarthritis Cartilage 10:119–126CrossRefGoogle Scholar
  22. Lawrence JS (1977) Rheumatism in populations. Heinemann, LondonGoogle Scholar
  23. Leal AM, Begona Ruiz-Larrea M, Martinez R, Lacort M (1998) Cytoprotective actions of estrogens against tert-butyl hydroperoxide-induced toxicity in hepatocytes. Biochem Pharmacol 56:1463–1469CrossRefGoogle Scholar
  24. Liang Y, Belford S, Tang F, Prokai L, Simpkins JW, Hughes JA (2001) Membrane fluidity effects of estratrienes. Brain Res Bull 54:661–668CrossRefGoogle Scholar
  25. Liehr JG, Roy D (1998) Pro-oxidant and antioxidant effects of estrogens. In: Armstrong D (ed) Free radical and antioxidant protocols. Humana, Totowa, pp 425–435Google Scholar
  26. Mattey DL, Nixon N, Alldersea JE, Cotton W, Fryer AA, Zhao L, Jones P, Strange RC (1993) Alpha, mu and pi class glutathione S-transferases in human synovium and cultured synovial fibroblasts: effects of interleukin-1 alpha, H2O2 and inhibition of eicosanoid synthesis. Free Rad Res Commun 19:159–171Google Scholar
  27. Mattson MP, Robinson N, Guo Q (1997) Estrogens stabilize mitochondrial function and protect neural cells against the pro-apoptotic action of mutant presenilin-1. Neuroreport 8:3817–3821Google Scholar
  28. Mazetti I, Grigolo B, Pulsatelli L, Dolzani P, Silvestri T, Roseti L, Meliconi R, Facchini A (2001) Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis. Clin Sci (Lond) 101:593–599Google Scholar
  29. Nevitt MC, Cummings SR, Lane NE, Hochberg MC, Scott JC, Pressman AR, Genant HK, Cauley JA (1996) Association of estrogen replacement therapy with the risk of osteoarthritis of the hip in elderly white women. Arch Intern Med 156:2073–2080CrossRefGoogle Scholar
  30. Rogers FB, Lansbury J (1956) Urinary gonadotrophin secretion in osteoarthritis. Am J Med Sci 232:419–420Google Scholar
  31. Sawada H, Masakazu I, Kihara T, Urushitani M, Akaike A, Shimohama S (1998) Estradiol protects mesencephalic dopaminergic neurons from oxidative stress-induced neuronal death. J Neurosci Res 54:707–719Google Scholar
  32. Schalwijk J, Berg WB van den, Putte LB van de, Joosten LA (1985) Hydrogen peroxide suppresses the proteoglycan synthesis of intact articular cartilage. J Rheumatol 12:205–210Google Scholar
  33. Schwartz Z, Gates PA, Nasatzky E, Sylvia VL, Mendez J, Dean DD, Boyan BD (1996) Effect of 17 beta-estradiol on chondrocyte membrane fluidity and phospholipid metabolism is membrane-specific, sex-specific, and cell maturation-dependent. Biochim Biophys Acta 1282:1–10Google Scholar
  34. Schwenke DC (1998) Aging, menopause, and free radicals. Semin Reprod Endocrinol 16:281–308Google Scholar
  35. Spector TD, Champion GD (1989) Generalised osteoarthritis: a hormonally mediated disease. Ann Rheum Dis 48:523–527Google Scholar
  36. Spector TD, Perry LA, Tubb G, Huskisson EC (1987) Androgen status of women with rheumatoid arthritis. Br J Rheumatol 26:316–318Google Scholar
  37. Spector TD, Perry LA, Jubb RW (1991) Endogenous sex steroid levels in women with generalised osteoarthritis. Clin Rheum 10:316–319Google Scholar
  38. Spector TD, Nandra D, Hart DJ, Doyle DV (1997) Is hormone replacement therapy protective for hand and knee osteoarthritis in women? The Chingford study. Ann Rheum Dis 56:432–434Google Scholar
  39. Strecker JR, Lauritzen C (1989) Praxis der Hormonbehandlung im Klimakterium. Bücherei Frauenarztes 29:9Google Scholar
  40. Suleimanov SS, Denisov IP, Sergeev PV (1985) Nature of the recognition system of uterine cell plasma membranes for estradiol. Farmakol Toksikol 48:58–61Google Scholar
  41. Tiku ML, Gupta S, Deshmukh DR (1999) Aggrecan degradation in chondrocytes is mediated by reactive oxygen species and protected by antioxidants. Free Rad Res 30:395–405Google Scholar
  42. Villarca A, Spatz M, Dodson RF, Corn C, Bembry J (1989) Effect of arachidonic acid on cultured cerebromicrovascular endothelium: permeability, lipid peroxidation and membrane “fluidity”. Acta Neuropathol 78:310–316CrossRefGoogle Scholar
  43. Wluka AE, Cicuttini FM, Spector TD (2000) Menopause, oestrogens and arthritis. Maturitas 35:183–199CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Institut für Anatomie und Zellbiologie der Martin-Luther-Universität Halle-WittenbergHalleGermany
  2. 2.Anatomisches Institut der Universität KielKielGermany

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