title: Role of endogenous and exogenous female sex hormones in arthritis and osteoporosis development in B10.Q-ncf1*/* mice with collagen-induced chronic arthritis.
abstract: BACKGROUND
  Collagen-induced arthritis (CIA) is an often-used murine model for human rheumatoid arthritis (RA). Earlier studies have shown potent anti-arthritic effects with the female sex hormone estradiol and the selective estrogen receptor modulator (SERM) raloxifene in CIA in DBA/1-mice. B10.Q-ncf1*/*mice are B10.Q mice with a mutated Ncf1 gene. In B10.Q-ncf1*/*mice, CIA develops as a chronic relapsing disease, which more accurately mimics human RA. We investigated the role of endogenous and exogenous sex steroids and raloxifene in the course of this model of chronic arthritis. We also examined whether treatment would prevent the development of inflammation-triggered generalized osteoporosis.
  
  
  METHODS
  Female B10.Q-ncf1*/*mice were sham-operated or ovariectomized, and CIA was induced. 22 days later, when 30% of the mice had developed arthritis, treatment with raloxifene, estradiol or vehicle was started, and the clinical disease was evaluated continuously. Treatment was continued until day 56 after immunization. At termination of the experiment (day 73), bone mineral density (BMD) was analyzed, paws were collected for histological examination, and sera were analyzed for markers of cartilage turnover and pro-inflammatory cytokines.
  
  
  RESULTS
  Raloxifene and estradiol treatment, as well as endogenous estrogen, decreased the frequency of arthritis, prevented joint destruction and countered generalized osteoporosis. These effects were associated with lower serum levels of the pro-inflammatory cytokine IL-6.
  
  
  CONCLUSIONS
  This is the first study to show that raloxifene and estradiol can ameliorate established erosive arthritis and inflammation-triggered osteoporosis in this chronic arthritis model. We propose that treatment with raloxifene could be a beneficial addition to the treatment of postmenopausal RA.
authors.affiliation: Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden. caroline.jochems@rheuma.gu.se
authors.forename: Caroline
authors.initials: C
authors.lastname: Jochems
authors.forename: Ulrika
authors.initials: U
authors.lastname: Islander
authors.forename: Malin
authors.initials: M
authors.lastname: Erlandsson
authors.forename: Cecilia
authors.initials: C
authors.lastname: Engdahl
authors.forename: Marie
authors.initials: M
authors.lastname: Lagerquist
authors.forename: Inger
authors.initials: I
authors.lastname: Gjertsson
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Hans
authors.initials: H
authors.lastname: Carlsten
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D004967:Estrogens / Q000502:physiology*; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics*; D019255:NADPH Oxidases / Q000235:genetics / Q000502:physiology*; D010003:Osteoarthritis / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D010052:Ovariectomy; D015995:Prevalence; D020849:Raloxifene Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D004967:Estrogens; D015850:Interleukin-6; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1