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.
Highlights
Postmenopausal women with rheumatoid arthritis (RA) have increased risk of developing osteoporosis due to chronic inflammation and estrogen deprivation
The present study show that Collagen antibody-induced arthritis (CAIA), a short reproducible arthritis model that is compatible with C57BL/6 mice, is associated with increased number of osteoclasts and trabecular bone loss
The complement system is important in arthritis development in CAIA [14], and the serum Complement factor 3 (C3) levels were increased by 31 % in CAIA mice compared with controls (Fig. 1c)
Summary
Postmenopausal women with rheumatoid arthritis (RA) have increased risk of developing osteoporosis due to chronic inflammation and estrogen deprivation. 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. The impact on bone of the CAIA model in C57BL/6 mice has not previously been studied. The aim of this study was to determine if CAIA can be used to study postmenopausal arthritis-induced osteoporosis. The susceptibility for CIA is poor in mice of C57BL/6 background, the commonly used strain for Grahnemo et al Arthritis Research & Therapy (2015) 17:189 development of osteoporosis in C57BL/6 mice with CAIA has never previously been investigated. The aim of this study was to determine whether CAIA is a suitable model for studies of postmenopausal arthritis-induced osteoporosis
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