Estrogen deficiency accelerates murine autoimmune arthritis associated with receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis

Tomoko Yoneda, Naozumi Ishimaru, Rieko Arakaki, Masaru Kobayashi, Takashi Izawa, Keiji Moriyama, Yoshio Hayashi

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

The aims of this study were to evaluate the in vivo effects of estrogen deficiency in MRL/lpr mice as a model for rheumatoid arthritis and to analyze the possible relationship between immune dysregulation and receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis. Experimental studies were performed in ovariectomized (Ovx)-MRL/lpr, Ovx-MRL+/+, sham-operated-MRL/ lpr, and sham-operated-MRL+/+ mice. Severe autoimmune arthritis developed in younger Ovx-MRL/lpr mice until 24 wk of age, whereas these lesions were entirely recovered by pharmacological levels of estrogen administration. A significant elevation in serum rheumatoid factor, anti-double-stranded DNA, and anti-type II collagen was found in Ovx-MRL/lpr mice and recovered in mice that underwent estrogen administration. A high proportion of CD4+ T cells bearing RANKL was found, and an enhanced expression of RANKL mRNA and an impaired osteoprotegerin mRNA was detected in the synovium. An increase in both osteoclast formation and bone resorption pits was found. These results indicate that estrogen deficiency may play a crucial role in acceleration of autoimmune arthritis associated with RANKL-mediated osteoclastogenesis in a murine model for rheumatoid arthritis.

Original languageEnglish
Pages (from-to)2384-2391
Number of pages8
JournalEndocrinology
Volume145
Issue number5
DOIs
Publication statusPublished - May 2004
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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