Abstract
The purpose of this study was to investigate whether serum levels of selected endogenous estrogens and their metabolites are involved in the pathogenesis of osteoarthritis in pre- and post-menopausal women with osteoarthritis. Sixty-four patients with osteoarthritis (OA) of the knee, 48 patients with rheumatoid arthritis (RA) of the knee, and 48 healthy women were included in this study. Serum concentrations of estradiol and estrogen metabolites, such as 2-hydroxyestrone, 2-hydroxyestradiol, and 16α-hydroxyestrone, were measured by high performance liquid chromatography-mass spectrometry. Our results show that the serum concentrations of free estradiol and total 2-hydroxyestrone were significantly lower in pre-menopausal women with OA compared to the levels detected in the control groups (RA and healthy women). While serum concentrations of free and total estradiol in post-menopausal women with OA was significantly decreased compared to those of the control groups, the level of total 2-hydroxyestradiol significantly increased in postmenopausal women. Furthermore, the total 2-hydroxyestrone concentration positively correlated with the total estradiol level in pre-menopausal women with OA. In addition, the total 2-hydroxyestradiol level positively correlated with free and total estradiol levels in post-menopausal women with OA. In conclusion, estradiol and estrogen metabolites, including 2-hydroxyestrone and 2-hydroxyestradiol, were found in the sera of pre- and post-menopausal women with OA. Except for free and total estradiol deficiency, a decreased serum level of total 2-hydroxyestrone in pre-menopausal women and an increased total 2-hydroxyestradiol level in post-menopausal women with OA may also correlate with the pathogenesis of female OA.
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Lachance L, Sowers MF, Jamadar D, Hochberg M. The natural history of emergent osteoarthritis of the knee in women. Osteoarthritis Cartilage 2002, 10: 849–54.
Cecil RL, Archer BH. Arthritis of the menopause. J Am Med Assoc 1925, 84: 75–9.
Wluka AE, Cicuttini FM, Spector TD. Menopause, oestrogens and arthritis [review]. Maturitas 2000, 35: 183–99.
Felson DT, Nevitt MC. The effects of estrogen on osteoarthritis. Curr Opin Rheumatol 1998, 10: 269–72.
Maheu E, Dreiser RL, Guillou GB, Dewailly J. Hand osteoarthritis patients characteristics according to the existence of a hormone replacement therapy. Osteoarthritis Cartilage 2000, 8 (Suppl A): S33–7.
Oliveria SA, Felson DT, Klein RA, Reed JI, Walker AM. Estrogen replacement therapy and the development of osteoarthritis. Epidemiology 1996, 7: 415–9.
Parazzini F; Progretto Menopausa Italia Study Group. Menopausal status, hormone replacement therapy use and risk of self-reported physician-diagnosed osteoarthritis in women attending menopause clinics in Italy. Maturitas 2003, 46: 207–12.
Fishman J. Aromatic hydroxylation of estrogens. Annu Rev Physiol 1983, 45: 61–72.
Lotinun S, Westerlind KC, Turner RT. Tissue-selective effects of continuous release of 2-hydroxyestrone and 16alpha-hydroxyestrone on bone, uterus and mammary gland in ovariectomized growing rats. J Endocrinol 2001, 170: 165–74.
Robinson JA, Waters KM, Turner RT, Spelsberg TC. Direct action of naturally occurring estrogen metabolites on human osteoblastic cells. J Bone Miner Res 2000, 15: 499–506.
MacLusky NJ, Riskalla M, Krey L, Parvizi N, Naftolin F. Anovulation in female rats induced by neonatal administration of the catechol estrogens, 2-hydroxy-estradiol and 4-hydroxy-estradiol. Neuroendocrinology 1983, 37: 321–7.
Tang M, Abplanalp W, Ayres S, Subbiah MT. Superior and distinct antioxidant effects of selected estrogen metabolites on lipid peroxidation. Metabolism 1996, 45: 411–4.
Lim SK, Won YJ, Lee JH, et al. Altered hydroxylation of estrogen in patients with postmenopausal osteopenia. J Clin Endocrinol Metab 1997, 82: 1001–6.
Hodge J, Roodman-Weiss J, Lyss C, Wagner D, Klug T, Civitelli R. Increased inactive estrogen metabolites in urine of early postmenopausal women with low bone density. J Bone Miner Res 1995, 10 (Suppl 1): S444.
Sowers MR, McConnell D, Jannausch M, Buyuktur AG, Hochberg M, Jamadar DA. Estradiol and its metabolites and their association with knee osteoarthritis. Athritis Rheum 2006, 54: 2481–7.
Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 1986, 29: 1039–49.
Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis 1957, 16: 494–502.
Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988, 31: 315–24.
Xu X, Roman JM, Issaq HJ, Keefer LK, Veenstra TD, Ziegler RG. Quantitative measurement of endogenous estrogens and estrogen metabolites in human serum by liquid chromatography-tandem mass spectrometry. Anal Chem 2007, 79: 7813–21.
Ham KD, Loeser RF, Lindgren BR, Carlson CS. Effects of long-term estrogen replacement therapy on osteoarthritis severity in cynomolgus monkeys. Arthritis Rheum 2002, 46: 1956–64.
Richmond RS, Carlson CS, Register TC, Shanker G, Loeser RF. Functional estrogen receptors inadult articular cartilage:estrogen replacement therapy increases chondrocyte synthesis of proteolycans and insulin-like growth factor binding protein 2. Arthritis Rheum 2000, 43: 2081–90.
Turner AS, Athanasiou KA, Zhu CF, Alvis MR, Bryant HU. Biochemical effects of estrogen on articular cartilage in ovariectomized sheep. Osteoarthritis Cartilage 1997, 5: 63–9.
Kinney RC, Schwartz Z, Week K, Lotz MK, Boyan BD. Human articular chondrocytes exhibit sexual dimorphism in their responses to 17 beta-estradiol. Osteoarthritis Cartilage 2005, 13: 330–7.
Englert C, Blunk T, Fierlbeck J, et al. Steroid hormones strongly support bovine articular cartilage integration in the absence of interleukin-1beta. Arthritis Rheum 2006, 54: 3890–7.
Høegh-Andersen P, Tankó LB, Andersen TL, et al. Ovariectomized rats as a model of postmenopausal osteoarthritis: validation and application. Arthritis Res Ther 2004, 6: R169–80.
Lee YJ, Lee EB, Kwon YE, et al. Effect of estrogen on the expression of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 and tissue inhibitor of metalloprotemase-1 in osteoarthritis chondrocytes. Rheumatol Int 2003, 23: 282–8.
Li J, Liao EY, Dai RC, Wei QY, Luo XH. Effects of 17 beta-estradiol on the expression of interstitial collagenases-8 and -13 (MMP-8 and MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in ovariectomized rat osteoblastic cells. J Mol Histol 2004, 35: 723–31.
Seeger H, Mueck AO, Lippert TH. Effect of estradiol metabolites on prostacyclin synthesis in human endothelial cell cultures. Life Sci 1999, 65: PL167–70.
Kelly RW, Abel MH. Catechol oestrogens stimulate and direct prostaglandin synthesis. Prostaglandins 1980, 20: 613–26.
Liehr JG. Dual role of oestrogens as hormones and pro-carcinogens: tumour initiation by metabolic activation of oestrogens. Eur J Cancer Prev 1997, 6: 3–10.
Saari H, Suomalainen K, Lindy O, Konttinen YT, Sorsa T. Activation of latent human neutrophil collagenase by reactive oxygen species and serine proteases. Biochem Biophys Res Commun 1990, 171: 979–87.
Thibodeau PA, Paquette B. DNA damage induced by catecholestrogens in the presence of copper (II): generation of reactive oxygen species and enhancement by NADH. Free Radic Biol Med 1999, 27: 1367–77.
Li Y, Trush MA, Yager JD. DNA damage caused by reactive oxygen species originating from a copper-dependent oxidation of the 2-hydroxy catechol of estradiol. Carcinogenesis 1994, 15: 1421–7.
Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro: implications for atherosclerotic plaque stability. J Clin Invest 1996, 98: 2572–9.
Paquette B, Bisson M, Therriault H, et al. Activation of matrix metalloproteinase-2 and -9 by 2- and 4-hydroxyestradiol. J Steroid Biochem Mol Biol 2003, 87: 65–73.
Sowers M. Epidemiology of risk factors for osteoarthritis: systemic factors. Curr Opin Rheumatol 2001, 13: 447–51.
Clarke R, Leonessa F, Welch JN, Skaar TC. Cellular and molecular pharmacology of antiestrogen action and resistance. Pharmacol Rev 2001, 53: 25–71.
Ushiyama T, Ueyama H, Inoue K, Ohkubo I, Hukuda S. Expression of genes for estrogen receptors alpha and beta in human articular chondrocytes. Osteoarthritis Cartilage 1999, 7: 560–6.
Richette P, Laborde K, Boutron C, Bardin T, Corvol MT, Savouret JF. Correlation between serum and synovial fluid estrogen concentrations: comment on the article by Sowers et al. Arthritis Rheum 2007, 56: 698–9.
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W. Gao and C. Zeng comtributed equally to this work.
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Gao, W., Zeng, C., Cai, D. et al. Serum concentrations of selected endogenous estrogen and estrogen metabolites in pre- and post-menopausal Chinese women with osteoarthritis. J Endocrinol Invest 33, 644–649 (2010). https://doi.org/10.1007/BF03346664
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DOI: https://doi.org/10.1007/BF03346664