Effects of a two-year health-enhancing physical activity program on skeletal muscle protein profiles in people with rheumatoid arthritis

Background Rheumatoid arthritis (RA) induces loss of muscle mass and impairments, which discourage physical activity. Consequently, RA is associated with decreased levels of exercise. Positive effects of exercise on physical and mental health without increasing pain or disease activity have been demonstrated but the influence of moderate-intensity physical activity on the molecular effects in skeletal muscle in people with RA remains unclear. In this pilot study we investigated the impact of a two-year health-enhancing physical activity (HEPA) program on protein profiles in skeletal muscle biopsies from people with RA based on a unique set of interdisciplinary variables. Methods Six people with RA participated. Muscle biopsies were taken from m. vastus lateralis, and perceived disease impact, anthropometrics and physical capacity tests were assessed at baseline and year 1 and 2. Mass spectrometry-based quantitative proteomics and immunohistochemistry analysis were employed to examine molecular changes in the skeletal muscle in response to long-term HEPA. Results The study participants had moderate to low adherence to the HEPA program, the perceived disease impact and anthropometric parameters were not altered. Among the physical capacity tests, the Timed-stands test showed a significant improvement after one year. Mean pressure pain threshold was significantly reduced after 1- and 2-year HEPA participation. Proteome analysis of the muscle biopsies showed an up-regulation of proteins in the mitochondrial respiratory chain and predicted increased ATP production and improved muscle contractility in response to HEPA. Molecular pathways identified by proteome analysis revealed correlations to pain variables. Conclusions Our results indicate that long-term physical activity in people with RA may up-regulate proteins in the mitochondrial respiratory chain predicting increased ATP production and muscle contractility similar to what has been reported in healthy young men and might have a positive impact on muscle tissue by decreased muscle cell death.