Trabecular bone loss in collagen antibody-induced arthritis

Abstract

IntroductionPostmenopausal women with rheumatoid arthritis (RA) have increased risk of developing osteoporosis due to chronic inflammation and estrogen deprivation. Collagen antibody-induced arthritis (CAIA), an experimental polyarthritis model representing the effector phase of arthritis, is mainly mediated by the innate immune system. Compared to the widely used collagen-induced arthritis model, CAIA is conveniently short and can be used in C57BL/6 mice, enabling studies with knock-out mice. However, the impact on bone of the CAIA model in C57BL/6 mice has not previously been studied. Therefore, the aim of this study was to determine if CAIA can be used to study postmenopausal arthritis-induced osteoporosis.MethodsCAIA was induced by administration of collagen-type II antibodies and lipopolysaccharide to ovariectomized female C57BL/6J mice. Control mice received lipopolysaccharide, but no antibodies. Nine days later, femurs were collected for high-resolution micro-CT and histomorphometry. Serum was used to assess cartilage breakdown and levels of complement. Frequencies of immune cell subsets from bone marrow and lymph nodes were analyzed by flow cytometery.ResultsTrabecular bone mass was decreased and associated with increased number of osteoclasts per bone surface in the CAIA model. Also, the frequency of interleukin-17+ cells in lymph nodes was increased in CAIA.ConclusionThe present study show that CAIA, a short reproducible arthritis model that is compatible with C57BL/6 mice, is associated with increased number of osteoclasts and trabecular bone loss.

Suppression of Experimental Arthritis and Associated Bone Loss by a Tissue-Selective Estrogen Complex

“…In accordance with preserved BMD, BZA/E2 reduced bone marrow preosteoclasts, defined as M-CSFR ϩ cells of the monocyte/macrophage population by using flow cytometry. Changes in levels of these bone marrow preosteoclasts have previously been reported to correspond with numbers of differentiated osteoclasts in situ in bone sections, as well as correspond with alterations in trabecular BMD, in mice with experimental arthritis (17,18). However, bone metabolism serum markers were not altered by any treatment in CIA, possibly due to the timing of serum sampling.…”

IL-17-producing γδT cells are regulated by estrogen during development of experimental arthritis

“…6A), and also reduced arthritis frequency at day 9 from 73% in the placebo group [29] to 0% in the E2 group (data not shown). Arthritis data from the placebo group, but not from the E2 group, has previously been published elsewhere [29]. IL-17 + γδT cells in lymph nodes draining the joints of CAIA mice were studied and E2 increased lymph node IL-17 + γδT cells also in this model (Fig.…”

“…Although arthritis was generally milder in CAIA compared with CIA, E2 potently inhibited arthritis severity (Fig. 6A), and also reduced arthritis frequency at day 9 from 73% in the placebo group [29] to 0% in the E2 group (data not shown). Arthritis data from the placebo group, but not from the E2 group, has previously been published elsewhere [29].…”

“…AUC was calculated for each group for statistical comparison (n = 13-15 mice/group). Arthritis data from the placebo group, but not from the E2 group, has been reported elsewhere [29]. (B) %IL-17 + γδT cells in lymph nodes of CAIA mice (n = 11-13 mice/group).…”

“…Arthritis severity was scored (0-3) for each paw, giving 12 points maximum per mouse in CIA and CAIA, in CIA defined as follows: 1 = swelling or erythema in one joint; 2 = swelling or erythema in two joints; 3 = severe swelling or erythema of more than two joints, or ankylosis of the entire paw. Arthritis scoring in CAIA, as well as arthritis data from the placebo CAIA group, has previously been described elsewhere [29].…”