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ABSTRACT: Postmenopausal patients with rheumatoid arthritis (RA) are often treated with corticosteroids. Loss of estrogen, the inflammatory disease and exposure to corticosteroids all contribute to the development of osteoporosis. Therefore, our aim was to investigate if addition of the selective estrogen receptor modulator raloxifene, or estradiol, could prevent loss of bone mineral density in ovariectomized and dexamethasone treated mice with collagen-induced arthritis (CIA).
Female DBA/1-mice were ovariectomized or sham-operated, and CIA was induced. Treatment with dexamethasone (Dex) (125 μg/d), estradiol (E2) (1 μg/d) or raloxifene (Ral) (120 μg/day) alone, or the combination of Dex + E2 or Dex + Ral, was started after disease onset, and continued until termination of the experiments. Arthritic paws were collected for histology and one of the femoral bones was used for measurement of bone mineral density.
Dex-treatment alone protected against arthritis and joint destruction, but had no effect on osteoporosis in CIA. However, additional treatment with either Ral or E2 resulted in completely preserved bone mineral density.
Addition of raloxifene or estradiol to dexamethasone-treatment in experimental postmenopausal polyarthritis prevents generalized bone loss.
Arthritis research & therapy 06/2011; 13(3):R96. · 4.27 Impact Factor
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ABSTRACT: Galectin 3, an endogenous β-galactoside-binding lectin, plays an important role in the modulation of immune responses. The finding that galectin 3 is present in the inflamed synovium in patients with rheumatoid arthritis suggests that the protein is associated with the pathogenesis of this disease. We undertook this study to investigate the influence of galectin 3 deficiency in a murine model of arthritis.
Wild-type (WT) and galectin 3-deficient (galectin 3(-/-) ) mice were subjected to antigen-induced arthritis (AIA) through immunization with methylated bovine serum albumin. The concentration of serum cytokines (interleukin-6 [IL-6] and tumor necrosis factor α [TNFα]) and antigen-specific antibodies was evaluated using a cytometric bead array platform and enzyme-linked immunosorbent assay (ELISA). Cellular IL-17 responses were examined by flow cytometry, ELISA, and enzyme-linked immunospot assay.
The joint inflammation and bone erosion of AIA were markedly suppressed in galectin 3(-/-) mice as compared with WT mice. The reduced arthritis in galectin 3(-/-) mice was accompanied by decreased levels of antigen-specific IgG and proinflammatory cytokines. The frequency of IL-17-producing cells in the spleen was reduced in galectin 3(-/-) mice as compared with WT mice. Exogenously added recombinant galectin 3 could partially restore the reduced arthritis and cytokines in galectin 3(-/-) mice.
Our findings show that galectin 3 plays a pathogenic role in the development and progression of AIA and that the disease severity is accompanied by alterations of antigen-specific IgG levels, systemic levels of TNFα and IL-6, and frequency of IL-17-producing T cells. To our knowledge, this is the first report of in vivo evidence that galectin 3 plays a crucial role in the development of arthritis.
Arthritis & Rheumatism 02/2011; 63(2):445-54. · 7.87 Impact Factor
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ABSTRACT: OBJECTIVE.: Galectin-3 (gal-3), an endogenous beta-galactoside-binding lectin, plays an important role in the modulation of immune responses. The finding that gal-3 is present in the inflamed synovium in patients with rheumatoid arthritis (RA) suggests that the protein is associated with the pathogenesis of this disease. We have thus investigated the influence of gal-3 deficiency (gal-3(-/-)) in a murine model of arthritis. METHODS.: Wild type (WT) and gal-3(-/-) mice were subjected to antigen-induced arthritis (AIA) through immunization with methylated bovine serum albumin (mBSA). The concentration of serum cytokines (IL-6 and TNF-α) and antigen-specific antibodies was evaluated using a cytometric bead array platform and ELISA. Cellular IL-17 responses were examined by flow cytometry, ELISA and ELISPOT. RESULTS.: Joint inflammation and bone erosion in AIA was markedly suppressed in gal-3(-/-) mice compared to WT mice. Reduced arthritis in gal-3(-/-) mice was accompanied with decreased levels of antigen-specific IgG and pro-inflammatory cytokines. The frequency of IL-17-producing cells in the spleen was reduced in gal-3 deficient mice compared to wild type mice. Exogenously added recombinant gal-3 could partially restore the reduced arthritis and cytokines in gal-3(-/-) mice. CONCLUSION.: We show that gal-3 plays a pathogenic role in development and progression of AIA and that the disease severity is accompanied with alterations of antigen-specific IgG, systemic levels of TNF-α and IL-6 as well as frequency of IL-17 producing T cells. To our knowledge, this is the first report providing in vivo evidence that gal-3 plays a crucial role in the development of arthritis.
Arthritis & Rheumatism 10/2010; · 7.87 Impact Factor
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ABSTRACT: T-helper 17 (Th17) cells are characterized by their production of interleukin-17 (IL-17) and have a role in the protection against infections and in certain inflammatory diseases. Humans who lack Th17 cells are more susceptible to Staphylococcus aureus infections compared to individuals having Th17 cells. S. aureus is part of the commensal skin microflora and also colonize the infant gut. To investigate whether UV-killed S. aureus would be more capable of inducing IL-17 than other commensal bacteria, we stimulated mononuclear cells from adults, infants, and newborns with various gram-positive and gram-negative commensal bacteria. IL-17 was produced from adult memory Th17 cells after stimulation with superantigen-producing S. aureus but not nonsuperantigenic S. aureus or other common commensal gut bacteria. Cells from newborns were poor IL-17 producers after stimulation with S. aureus, whereas in some cases IL-17 was secreted from cells isolated from infants at the age of 4 and 18 months. These results suggest that superantigenic S. aureus are particularly efficient in stimulating IL-17 production and that the cytokine is produced from memory T cells.
Infection and immunity 10/2009; 78(1):381-6. · 4.21 Impact Factor
