Association of myostatin, a cytokine released by muscle, with inflammation in rheumatoid arthritis

Abstract

Myostatin is a cytokine produced and released by myocytes that might have an outstanding role not only in muscle wasting during cachexia but also in inflammation. Herein we explore the association between myostatin levels and inflammatory parameters in rheumatoid arthritis (RA). One hundred twenty-seven women without rheumatic diseases and 84 women with a diagnosis of RA were assessed in a cross-sectional study. Outcomes reflecting the activity of the arthritis including Disease Activity Score (DAS28-ESR) and impairment in functioning by the Health Assessment Questionnaire-Disability Index were assessed in RA. We obtained Skeletal muscle mass index (SMI), fat-free mass index (FFMI), and fat mass index using dual-energy x-ray absorptiometry. Serum myostatin was determined by enzyme-linked immunosorbent assay. Myostatin levels were correlated with disease activity and parameters of muscle mass. The SMI was lower and concentration of myostatin was higher in RA patients than in controls (P = .008 and P < .001, respectively). Myostatin significantly positively correlated with C-reactive protein (rho = 0.48, P < .001), erythrocyte sedimentation rate (rho = 0.28, P = .009), and DAS28-ESR (rho = 0.22, P = .04), and negatively correlated with SMI (rho = −0.29, P = .008), (FFMI) (rho = −0.24, P = .027). In the multivariate logistic regression analysis, levels of myostatin remained associated with disease activity in RA (P = .027). In our study, myostatin was associated with disease activity in RA patients, suggesting a mechanistic link between myostatin, muscle wasting and inflammation in RA.

Myostatin Levels and the Risk of Myopenia and Rheumatoid Cachexia in Women with Rheumatoid Arthritis

“…Other studies have demonstrated overexpression of myostatin in the synovial tissue of RA patients [ 37 , 40 ]. However, an increase in the serum levels of this myokine has also been reported by us in RA, mainly in patients with moderate or severe disease activity [ 10 ].…”

“…Santo et al found a prevalence from 13% to 30% in RA patients [ 29 ]. In this context, we previously reported a prevalence of rheumatoid cachexia of 14% in one study with a smaller sample of RA patients [ 10 ]. These differences in prevalence can be explained in part by the method of body composition assessment (DXA vs. bioelectrical impedance analysis or anthropometric measurements), the cut-offs used for diagnosis, the presence of comorbid diseases, and the disease characteristics of RA that can increase the risk of developing this condition (such as early vs. longer disease duration and a severe inflammatory status).…”

“…To date, there is growing interest from physicians and researchers regarding the effects of myostatin on skeletal muscle in patients with chronic diseases. Regarding RA, some works have investigated the relationship of myostatin with some relevant clinical variables [ 10 – 12 ]. Recently, we identified a relationship between high serum concentrations of myostatin and an increase in joint inflammation as well as a decrease in skeletal muscle mass in patients with RA [ 10 ].…”

“…Regarding RA, some works have investigated the relationship of myostatin with some relevant clinical variables [ 10 – 12 ]. Recently, we identified a relationship between high serum concentrations of myostatin and an increase in joint inflammation as well as a decrease in skeletal muscle mass in patients with RA [ 10 ]. However, that study had an insufficient sample size to evaluate whether a cut-off value for high myostatin levels could help to identify myopenia or to demonstrate an increase in the risk of rheumatoid cachexia [ 10 ].…”

“…Recently, we identified a relationship between high serum concentrations of myostatin and an increase in joint inflammation as well as a decrease in skeletal muscle mass in patients with RA [ 10 ]. However, that study had an insufficient sample size to evaluate whether a cut-off value for high myostatin levels could help to identify myopenia or to demonstrate an increase in the risk of rheumatoid cachexia [ 10 ]. To date, the relevance of elevated levels of this myokine in the myopenia observed in RA patients has not been proven, and some authors have reported conflicting results, making it difficult to determine the clinical value of serum myostatin; for example, Wada et al observed that lower myostatin levels were associated with myopenia in patients with RA [ 11 ], while in an abstract published by Silva et al, there was no correlation found between myostatin concentrations and the quantity of appendicular lean mass or the fat mass indices [ 12 ].…”