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

Jochems, C; Islander, U; Erlandsson, M; Engdahl, C; Lagerquist, M; Ohlsson, C; Kutty Selva, Nandakumar LU ; Holmdahl, Rikard LU and Carlsten, H (2011) In Clinical and Experimental Immunology 165(1). p.121-129
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
BMD, CAIA, CIA, oestradiol, luciferase-ERE, ovariectomy, raloxifene
in
Clinical and Experimental Immunology
volume
165
issue
1
pages
121 - 129
publisher
British Society for Immunology
external identifiers
  • wos:000291224600014
  • pmid:21501150
  • scopus:79958170434
ISSN
0009-9104
DOI
10.1111/j.1365-2249.2011.04397.x
language
English
LU publication?
yes
id
9e35955b-fff9-4275-a58c-1c70609feec9 (old id 1936964)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21501150?dopt=Abstract
date added to LUP
2012-01-19 10:33:50
date last changed
2017-01-01 04:00:08
@article{9e35955b-fff9-4275-a58c-1c70609feec9,
  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.},
  author       = {Jochems, C and Islander, U and Erlandsson, M and Engdahl, C and Lagerquist, M and Ohlsson, C and Kutty Selva, Nandakumar and Holmdahl, Rikard and Carlsten, H},
  issn         = {0009-9104},
  keyword      = {BMD,CAIA,CIA,oestradiol,luciferase-ERE,ovariectomy,raloxifene},
  language     = {eng},
  number       = {1},
  pages        = {121--129},
  publisher    = {British Society for Immunology},
  series       = {Clinical and Experimental Immunology},
  title        = {Effects of oestradiol and raloxifene on the induction and effector phases of experimental postmenopausal arthritis and secondary osteoporosis.},
  url          = {http://dx.doi.org/10.1111/j.1365-2249.2011.04397.x},
  volume       = {165},
  year         = {2011},
}