Estrogen deficiency accelerates murine autoimmune arthritis associated with receptor activator of nuclear factor-kappa B ligand-mediated osteoclastogenesis.
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-kappaB 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.
Yoneda
Tomoko
T
Department of Pathology, Tokushima University School of Dentistry, Tokushima 770-8504, Japan.
Ishimaru
Naozumi
N
Arakaki
Rieko
R
Kobayashi
Masaru
M
Izawa
Takashi
T
Moriyama
Keiji
K
Hayashi
Yoshio
Y
D000818:Animals; D001168:Arthritis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001172:Arthritis, Rheumatoid; D001327:Autoimmune Diseases / Q000503:physiopathology*; D001862:Bone Resorption; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D004967:Estrogens / Q000172:deficiency* / Q000502:physiology; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics; D007596:Joints / Q000473:pathology; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D010010:Osteoclasts / Q000502:physiology*; D053244:Osteoprotegerin; D010052:Ovariectomy; D053245:RANK Ligand; D012333:RNA, Messenger / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D016207:Cytokines; D004967:Estrogens; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9