FRI0768-HPR Muscle wasting in osteoarthritis model induced by anterior cruciate ligament transection
Authors: JMDS Silva, PVG Alabarse, VDON Teixeira, EC Freitas, FH de Oliveira, RMDS Chakr, RM Xavier
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteoarthritis (OA) is a chronic joint disease characterized by progressive loss of articular cartilage and abnormal bone formation. Furthermore, there are changes in periarticular muscles, such as loss of muscle mass, strength and function. These features may contribute to functional impairment among patients. <h3>Objectives</h3> This study aimed to investigate the molecular pathways involved in muscle wasting in an animal model of OA induced by anterior cruciate ligament (ACL) transection in rats. <h3>Methods</h3> Female Wistar rats were allocated into two groups: OA (submitted to the ACL transection; n=9) and SHAM (submitted to surgical procedures without ACL transection; n=8) [1]. Spontaneous exploratory locomotion, nociception and body weight of animals were evaluated weekly. Twelve weeks after the disease induction, animals were euthanized and the right knee joints were collected for further confirmation of the disease by histopathology, accordingly to OARSI histologic scoring system [2]. Gastrocnemius muscle from the right hind paw were dissected and weighed. Gastrocnemius was used for evaluation of muscle atrophy [3] and protein expression of myostatin, MuRF-1, MyoD and myogenin. Data were compared by Student9s t test or ANOVA followed by Tukey9s test or ANOVA followed by Mann–Whitney9s U-test. The results are expressed as mean values ± standard deviation (SD) for symmetric variables and as medians with interquartile range for asymmetric variables. Significance was accepted at P&lt;0.05. <h3>Results</h3> Histopathology of the right knee joints confirmed the development of the disease in animals from OA group. Gastrocnemius area of animals from OA group had a reduction of about 10% compared to animals from SHAM group. Protein expression of myostatin was increased in OA group, while myogenin expression was decreased. MuRF-1 and MyoD expression was similar in both OA and SHAM groups. Spontaneous exploratory locomotion, nociception, body weight and weight of gastrocnemius showed no difference between OA and SHAM groups. <h3>Conclusions</h3> Gastrocnemius atrophy in OA induced by ACL transection involves increased protein expression of myostatin and decreased protein expression of myogenin. In this model, muscle wasting may be linked to myostatin-induced deficits in satellite-cell differentiation due to decreased expression of myogenin. <h3>References</h3> Elsaid KA, Machan JT, Waller K, Fleming BC, Jay GD. The Impact of Anterior Cruciate Ligament Injury on Lubricin Metabolism and the Effect of Inhibiting Tumor Necrosis Factor alpha on Chondroprotection in an Animal Model. Arthritis and Rheumatism. 2009;60(10):2997–3006. Gerwin N, Bendele AM, Glasson S, Carlson CS. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat. Osteoarthritis and Cartilage. 2010;18:S24-S34. Filippin LI, Teixeira VN, Viacava PR, Lora PS, Xavier LL, Xavier RM. Temporal development of muscle atrophy in murine model of arthritis is related to disease severity. Journal of Cachexia Sarcopenia and Muscle. 2013;4(3):231–8. de Oliveira Nunes Teixeira V, Filippin LI, Viacava PR, de Oliveira PG, Xavier RM. Muscle wasting in collagen-induced arthritis and disuse atrophy. Exp Biol Med (Maywood). 2013;238(12):1421–30. <h3>Disclosure of Interest</h3> None declared