This Article Full Text Full Text (PDF) All Versions of this Article: 145/5/2384    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yoneda, T. Articles by Hayashi, Y. Search for Related Content PubMed PubMed Citation Articles by Yoneda, T. Articles by Hayashi, Y.

Estrogen Deficiency Accelerates Murine Autoimmune Arthritis Associated with Receptor Activator of Nuclear Factor-B Ligand-Mediated Osteoclastogenesis

Departments of Pathology (T.Y., N.I., R.A., M.K., T.I., Y.H.) and Orthodontics (T.Y., T.I., K.M.), Tokushima University School of Dentistry, Tokushima 770-8504 Japan

Address all correspondence and requests for reprints to: Dr. Yoshio Hayashi, Department of Pathology, Tokushima University School of Dentistry, 3 Kuramotocho, Tokushima 770-8504, Japan. E-mail: hayashi{at}dent.tokushima-u.ac.jp.

The aims of this study were to evaluate the in vivo effects of estrogen deficiency in MRL/lpr mice as a model for rheumatoid arthritis and to analyze the possible relationship between immune dysregulation and receptor activator of nuclear factor-B ligand (RANKL)-mediated osteoclastogenesis. Experimental studies were performed in ovariectomized (Ovx)-MRL/lpr, Ovx-MRL+/+, sham-operated-MRL/lpr, and sham-operated-MRL+/+ mice. Severe autoimmune arthritis developed in younger Ovx-MRL/lpr mice until 24 wk of age, whereas these lesions were entirely recovered by pharmacological levels of estrogen administration. A significant elevation in serum rheumatoid factor, anti-double-stranded DNA, and anti-type II collagen was found in Ovx-MRL/lpr mice and recovered in mice that underwent estrogen administration. A high proportion of CD4⁺ T cells bearing RANKL was found, and an enhanced expression of RANKL mRNA and an impaired osteoprotegerin mRNA was detected in the synovium. An increase in both osteoclast formation and bone resorption pits was found. These results indicate that estrogen deficiency may play a crucial role in acceleration of autoimmune arthritis associated with RANKL-mediated osteoclastogenesis in a murine model for rheumatoid arthritis.

This article has been cited by other articles:

				A. E. Kearns, S. Khosla, and P. J. Kostenuik Receptor Activator of Nuclear Factor {kappa}B Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease Endocr. Rev., April 1, 2008; 29(2): 155 - 192. [Abstract] [Full Text] [PDF]

				R. H. Straub The Complex Role of Estrogens in Inflammation Endocr. Rev., August 1, 2007; 28(5): 521 - 574. [Abstract] [Full Text] [PDF]

				A. R. Pettit, N. C. Walsh, C. Manning, S. R. Goldring, and E. M. Gravallese RANKL protein is expressed at the pannus-bone interface at sites of articular bone erosion in rheumatoid arthritis Rheumatology, September 1, 2006; 45(9): 1068 - 1076. [Abstract] [Full Text] [PDF]

				A. Bhattacharya, M. Rahman, J. Banu, R. A. Lawrence, H. S. McGuff, I.R. Garrett, M. Fischbach, and G. Fernandes Inhibition of Osteoporosis in Autoimmune Disease Prone MRL/Mpj-Faslpr Mice by N-3 Fatty Acids J. Am. Coll. Nutr., June 1, 2005; 24(3): 200 - 209. [Abstract] [Full Text] [PDF]

				X.-c. Bai, D. Lu, A.-l. Liu, Z.-m. Zhang, X.-m. Li, Z.-p. Zou, W.-s. Zeng, B.-l. Cheng, and S.-q. Luo Reactive Oxygen Species Stimulates Receptor Activator of NF-{kappa}B Ligand Expression in Osteoblast J. Biol. Chem., April 29, 2005; 280(17): 17497 - 17506. [Abstract] [Full Text] [PDF]