Session Title: Rheumatoid Arthritis: Animal Models
Session Type: Abstract Submissions (ACR)
Background/Purpose: Patients with rheumatoid arthritis (RA) have a high risk of osteoporosis and osteoporotic fracture. In addition to the primary risk factors for osteoporosis, osteoporosis in RA is characterized by a complexity of other risk factors, including inflammation, immobilization, and use of corticosteroids. Anti-human interleukin-6 (IL-6) receptor antibody and various TNF inhibitors have an excellent therapeutic effect on RA symptoms, such as inflammation, pain, and swelling of joints. However, it is not fully understood whether inhibition of IL-6 and TNF-α can improve osteoporosis in patients with RA. Here, we investigated the interaction between proinflammatory cytokines and bone loss, using glucose-6-phosphate isomerase (GPI)-induced arthritis.
Methods: GPI-induced arthritis in DBA/1J mice was triggered by intradermal injection of recombinant GPI. Mice were injected once with anti-mouse IL-6 receptor antibody (MR16-1) intraperitoneally 5 days after immunization. On the other hand, TNF receptor-Fc (TNFR-Fc) was given intraperitoneally 3 times per week from the 5th day of immunization. The femurs of mice were harvested at various time points and the lumbar spine was excised at day 35. The trabecular bone volume (BV/TV) of the femurs and the lumbar spine was analyzed by using micro-computed tomography (μCT).
Results: First, we examined the severity of bone loss in GPI-induced arthritis. In immunized mice, BV/TV of femurs had significantly declined by 32.5% on day 7 (beginning of swelling) and by 61.5% on day 14 (peak of swelling) compared with non-immunized mice. Thereafter, as the swelling decreased, BV/TV of femurs in immunized mice was gradually recovered to 61.0% of non-immunized mice by day 35. Because arthritis significantly decreased the bone volume of femurs in mice, we next examined the involvement of IL-6 and TNF-α in bone loss in GPI-induced arthritis. Both MR16-1 and TNFR-Fc significantly suppressed the development of arthritis compared with untreated immunized mice. In MR16-1-treated mice, BV/TV of femurs and lumbar spine on day 35 was significantly increased to 1.3-fold and 1.2-fold that in untreated arthritic mice. On the other hand, TNFR-Fc increased the bone volume of femurs to 1.2-fold, but it did not affect that of the lumbar spine.
Conclusion: We demonstrated that IL-6 and TNF-α play a crucial role in bone loss of femurs caused by inflammatory arthritis in mice. However, in the lumbar spine, IL-6 is involved in bone loss but TNF-α is not. This suggests that blockade of IL-6 would have a beneficial effect on systemic osteoporosis in RA patients.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-interleukin-6-receptor-antibody-improves-systemic-osteoporosis-in-a-mice-model-of-glucose-6-phosphate-isomerase-induced-arthritis/