Paula Ramos Viacava

Muscle wasting in collagen-induced arthritis and disuse atrophy

The mechanisms of muscle wasting and decreased mobility have a major functional effect in rheumatoid arthritis, but they have been poorly studied. The objective of our study is to describe muscular involvement and the pathways in an experimental model of arthritis compared to the pathways in disuse atrophy. Female Wistar rats were separated into three groups: control (CO), collagen-induced arthritis (CIA), and immobilized (IM). Spontaneous locomotion and weight were evaluated weekly. The gastrocnemius muscle was evaluated by histology and immunoblotting to measure the expression of myostatin (a negative regulator), LC3 (autophagy), MuRF-1 (proteasome-mediated proteolysis), MyoD, and myogenin (satellite-cell activation). The significance level was set at P < 0.05, and histological analysis of joints confirmed the severity of the arthropathy. There was a significant difference in spontaneous locomotion in the CIA group. Animal body weight, gastrocnemius muscle weight, and relative muscle weight decreased 20%, 30%, and 20%, respectively, in the CIA rats. Inflammatory infiltration and swelling were present in the gastrocnemius muscles of the CIA rats. The mean cross-sectional area was reduced by 30% in the CIA group and by 60% in the IM group. The expressions of myostatin and LC3 between the groups were similar. There was increased expression of MuRF-1 in the IM (1.9-fold) and CIA (3.1-fold) groups and of myogenin in the muscles of the CIA animals (1.7-fold), while MyoD expression was decreased in the IM (20%) rats. This study demonstrated that the development of experimental arthritis is associated with decreased mobility, body weight, and muscle loss. Both IM and CIA animal models presented muscle atrophy, but while proteolysis and the regeneration pathways were activated in the CIA model, there was no activation of regeneration in the IM model. We can assume that muscle atrophy in experimental arthritis is associated with the disease itself and not simply with decreased mobility.

AB0101 Effect of aerobic exercise in experimental model of arthritis

Background Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease of unknown etiology, affecting not only the joints but also other tissues such as skeletal muscle [1]. Muscle loss is a secondary manifestation that impairs the function and quality of life of patients with RA [1]. Physical exercise is associated with reduced morbidity and other beneficial effects inseveral diseases [2, 3]. Objectives To evaluate the effect of aerobic exercise on muscle loss of animals with collagen-induced arthritis (CIA). Methods CIA was inducedin male mice DBA/1J asdescribed by Brand, 2010 [4]. The animals were divided into two CIA groups: (i) animals with exercise (protocol: walking for 30 min, from 9 to 15 m.min-1, three times a week for 4 weeks after the onset of the disease), (ii) animals without exercise. Clinical score and paw swelling were assessed daily during all the experimental period. The weight of the animals and spontaneous exploratory locomotion were evaluated weekly. After death, the myofiber area of the tibialis anterior and gastrocnemius muscles were evaluated as well as ankle joint histopathology. For statistical analysis, t-test were performed and statistical significance was considered for p values p<.05. Results No significant difference was observed in clinical parameters of disease activity (clinical score, paw swelling and animal weight) and spontaneous locomotion in the walking group compared with the group without exercise. Although not significant, exercise slightly decreased joint inflammation (1.6 ± 0.17 and 1.9 ± 0.20 arbitrary value, p=.16) and bone erosion (1.3 ± 0.26 and 1.8 ± 0.23 arbitrary value, p=.12), besides that, cartilage erosion were significantly reduced in exercised joint (1.3 ± 0.26 and 1.8 ± 0.23 arbitrary value, p<.05). However, there was significant difference in the myofiber sectional area: exercised CIA showed greater myofiber cross-sectional area compared to the group without exercise (598 ± 58 μm2 and 481 ± 63 μm2, respectively, p<.05), representing a difference of 24%. Conclusions This is the first intervention study with forced walk in the experimental model CIA. According to results, aerobic exercise applied from the first clinical signs showed benefit over cartilage erosion and muscle atrophy in an experimental model of arthritis, observed mainly by the reduction of myofiber area, but does not seem to impact in the process of arthritis. References McInnes IB, Schett G. New England Journal of Medicine 2011, 365(23). Navarro F et al. Cell Biochemistry and Function 2010, 28(4):266-273. Nader GA, Lundberg IE. Current Opinion in Rheumatology 2009, 21(6):599-603. Brand DD et al. Nature Protocols 2007, 2(5):1269-1275. Disclosure of Interest None Declared