Effects of oestradiol and raloxifene on the induction and effector phases of experimental postmenopausal arthritis and secondary osteoporosis.

Abstract

Oestradiol and the selective oestrogen receptor modulator (SERM) raloxifene have been shown to ameliorate collagen-induced arthritis (CIA) in rats and in mice. One aim was to investigate if raloxifene exerts its anti-arthritic and anti-osteoporotic effects during the induction or effector phase of arthritis. A second aim was to analyse if raloxifene activates the oestrogen response element (ERE) to produce its immune-modulator effects. CIA or collagen-antibody-induced arthritis (CAIA) was induced in ovariectomized DBA/1-mice. CIA was used for evaluation of treatment during the induction, and CAIA for the effector phase of arthritis and osteoporosis development. Raloxifene, oestradiol or vehicle was administered 5 days/week. The clinical disease was evaluated continuously. Bone marrow density (BMD) was analysed with peripheral quantitative computer tomography, paws were collected for histological examination, and sera were analysed for markers of bone and cartilage turnover and proinflammatory cytokines. Transgenic luciferase (Luc)-ERE mice were immunized with collagen (CII), and after 10 days injected once with raloxifene, oestradiol or vehicle before termination. Spleens were analysed for luciferase activity to measure ERE activation. Treatment with oestradiol or raloxifene during the induction phase of CIA failed to affect arthritis. Raloxifene did not hamper disease activity in CAIA, whereas oestradiol delayed the onset and ameliorated the severity. Both raloxifene and oestradiol preserved BMD in CAIA. CII-immunization increased the oestradiol-induced ERE activation in spleen, and raloxifene activated the ERE at about 25% the intensity of oestradiol. Further experiments are needed to elucidate the exact mechanisms behind this finding.

• Authors: C Jochems, U Islander, M Erlandsson, C Engdahl, M Lagerquist, C Ohlsson, K S Nandakumar, R Holmdahl, H Carlsten
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 165 Issue 1 Pg. 121-9 (Jul 2011) ISSN: 1365-2249 [Electronic] England
• PMID: 21501150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

Chemical References

• Antibodies
• Biomarkers
• Selective Estrogen Receptor Modulators
• Raloxifene Hydrochloride
• Estradiol
• Collagen

Topics

• Animals
• Antibodies (administration & dosage)
• Arthritis, Experimental (chemically induced, complications, drug therapy, immunology)
• Biomarkers (blood)
• Bone Marrow (pathology)
• Collagen (administration & dosage, immunology)
• Disease Progression
• Estradiol (administration & dosage)
• Female
• Humans
• Immunomodulation
• Mice
• Mice, Inbred DBA
• Mice, Transgenic
• Osteoporosis, Postmenopausal (complications, drug therapy, etiology, immunology)
• Ovariectomy
• Raloxifene Hydrochloride (administration & dosage)
• Response Elements (genetics)
• Selective Estrogen Receptor Modulators (administration & dosage)
• Transgenes (genetics)