title: Role of 2-methoxyestradiol as inhibitor of arthritis and osteoporosis in a model of postmenopausal rheumatoid arthritis.
abstract: In postmenopausal rheumatoid arthritis, both the inflammatory disease and estrogen deficiency contribute to the development of osteoporosis. As hormone replacement therapy is no longer an option, we hypothesized that 2-methoxyestradiol (2me2) could be beneficial, and asked if such therapy was associated with effects on reproductive organs. Mice were ovariectomized and arthritis was induced, whereafter mice were administered 2me2, estradiol, or placebo. Clinical and histological scores of arthritis, together with bone mineral density were evaluated. Uteri weight, reactive oxygen species (ROS) from spleen cells, and characterization of cells from joints and lymph nodes were analyzed. In addition, in vivo activation of estrogen response elements (ERE) by 2me2 was evaluated. Treatment with 2me2 and estradiol decreased the frequency and severity of arthritis and preserved bone. Joint destruction was reduced, neutrophils diminished and ROS production decreased. The uterine weight increased upon long-term 2me2 exposure, however short-term exposure did not activate ERE in vivo.
authors: Center for Bone and Arthritis Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. alexandra.stubelius@rheuma.gu.se
authors: Alexandra
authors: A
authors: Stubelius
authors: Emil
authors: E
authors: Andréasson
authors: Anna
authors: A
authors: Karlsson
authors: Claes
authors: C
authors: Ohlsson
authors: Asa
authors: A
authors: Tivesten
authors: Ulrika
authors: U
authors: Islander
authors: Hans
authors: H
authors: Carlsten
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D001169:Arthritis, Experimental / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000517:prevention & control*; D004195:Disease Models, Animal; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008811:Mice, Inbred DBA; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010052:Ovariectomy
chemical_list: D004958:Estradiol; D000077584:2-Methoxyestradiol