Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability.
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BACKGROUND: To identify molecular alterations in skeletal muscle in rheumatoid arthritis (RA) that may contribute to ongoing disability in RA. METHODS: Persons with seropositive or erosive RA (n = 51) and control subjects matched for age, gender, race, body mass index (BMI), and physical activity (n = 51) underwent assessment of disease activity, disability, pain, physical activity and thigh muscle biopsies. Muscle tissue was used for measurement of pro-inflammatory markers, transcriptomics, and comprehensive profiling of metabolic intermediates. Groups were compared using mixed models. Bivariate associations were assessed with Spearman correlation. RESULTS: Compared to controls, patients with RA had 75% greater muscle concentrations of IL-6 protein (p = 0.006). In patients with RA, muscle concentrations of inflammatory markers were positively associated (p < 0.05 for all) with disease activity (IL-1β, IL-8), disability (IL-1β, IL-6), pain (IL-1β, TNF-α, toll-like receptor (TLR)-4), and physical inactivity (IL-1β, IL-6). Muscle cytokines were not related to corresponding systemic cytokines. Prominent among the gene sets differentially expressed in muscles in RA versus controls were those involved in skeletal muscle repair processes and glycolytic metabolism. Metabolic profiling revealed 46% higher concentrations of pyruvate in muscle in RA (p < 0.05), and strong positive correlation between levels of amino acids involved in fibrosis (arginine, ornithine, proline, and glycine) and disability (p < 0.05). CONCLUSION: RA is accompanied by broad-ranging molecular alterations in skeletal muscle. Analysis of inflammatory markers, gene expression, and metabolic intermediates linked disease-related disruptions in muscle inflammatory signaling, remodeling, and metabolic programming to physical inactivity and disability. Thus, skeletal muscle dysfunction might contribute to a viscous cycle of RA disease activity, physical inactivity, and disability.
Published Version (Please cite this version)10.1186/s13075-016-1215-7
Publication InfoHuffman, Kim M; Jessee, Ryan; Andonian, Brian; Davis, Brittany N; Narowski, Rachel; Huebner, Janet L; ... Kraus, William E (2017). Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability. Arthritis Res Ther, 19(1). pp. 12. 10.1186/s13075-016-1215-7. Retrieved from https://hdl.handle.net/10161/13703.
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Assistant Professor of Medicine
Associate Professor of Medicine
Determining the role of physical activity in modulating health outcomes (cardiovascular disease risk) in persons with rheumatologic diseases (rheumatoid arthritis, gout, osteoarthritis) Integrating clinical rheumatology, basic immunology, metabolism, and exercise science in order to reduce morbidity in individuals with arthritis Evaluating relationships between circulating and intra-muscular metabolic intermediates and insulin resistance in sedentary as well as indiv
Associate Professor in Medicine
My research is focused on 1) understanding metabolic perturbations that occur in subpopulations of skeletal muscle mitochondria in response to a chronic high lipid environment, 2) identifying specific metabolites of lipid-induced mitochondrial stress that contribute to skeletal muscle insulin resistance and type II diabetes, and 3) understanding how mitochondrial adaptations in response to exercise confer protection against lipid-induced mitochondrial dysfunction.
Professor of Medicine
My special area of expertise is as a clinician scientist investigating osteoarthritis. Osteoarthritis is the most common form of joint disease in man and its incidence increases with age. It is a problem of increasing concern to the medical community due to the increasing longevity of the population. Trained as a molecular biologist and a Rheumatologist, I endeavor to study this disease from bedside to bench. The work in this laboratory focuses on osteoarthritis and deals w
Richard and Pat Johnson University Distinguished Professor
My training, expertise and research interests range from human integrative physiology and genetics to animal exercise models to cell culture models of skeletal muscle adaptation to mechanical stretch. I am trained clinically as an internist and preventive cardiologist, with particular expertise in preventive cardiology and cardiac rehabilitation. My research training spans molecular biology and cell culture, molecular genetics, and integrative human exercise physiology and metabolism. I pr
Professor of Medicine
Deb Muoio is a Professor of Medicine, Division of Endocrinology, and Director of Basic Research at the Duke Molecular Physiology Institute. She earned a PhD in Nutritional Biochemistry at the University of North Carolina, Chapel Hill, followed by postdoctoral fellowships at East Carolina and Duke Universities working in the areas of muscle physiology and metabolic disease. Her laboratory studies mechanisms of metabolic control and molecular events that link nutrition and exercise to health ou
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