Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability.
Abstract
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.
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https://hdl.handle.net/10161/13703Published Version (Please cite this version)
10.1186/s13075-016-1215-7Publication Info
Huffman, 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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Brian Andonian
Assistant Professor of Medicine
Brian Gilmore
House Staff
Kim Marie Huffman
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 individu
Timothy Robert Koves
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.
Virginia Byers Kraus
Mary Bernheim Distinguished Professor of Medicine
Virginia Byers Kraus, MD, PhD, is the Mary Bernheim Distinguished Professor of Medicine,
Professor of Orthopaedic Surgery, Professor of Pathology and a faculty member of the
Duke Molecular Physiology Institute in the Duke University School of Medicine. She
is a practicing Rheumatologist with over 30 years’ experience in translational musculoskeletal
research focusing on osteoarthritis, the most common of all arthritides. She trained
at Brown University (ScB 1979), Duke University (MD 19
William Erle Kraus
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
Deborah Marie Muoio
George Barth Geller Distinguished Professor of Cardiovascular Disease
Deb Muoio is professor in the Departments of Medicine and Pharmacology & Cancer Biology,
George Barth Geller Distinguished Professor of Cardiovascular Disease, and Associate
Director of the Duke Molecular Physiology Institute (DMPI). She is viewed nationally
and internationally as a leader in the fields of diabetes, obesity, exercise physiology,
and mitochondrial energy metabolism. Her laboratory investigates mechanisms of metabolic
regulation, with emphasis on molecular events that link
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