Show simple item record

Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability.

dc.contributor.author Andonian, Brian
dc.contributor.author Campbell, M
dc.contributor.author Davis, BN
dc.contributor.author Gilmore, BF
dc.contributor.author Hubal, MJ
dc.contributor.author Huebner, JL
dc.contributor.author Huffman, Kim Marie
dc.contributor.author Jessee, Ryan
dc.contributor.author Koves, TR
dc.contributor.author Kraus, Virginia Byers
dc.contributor.author Kraus, William Erle
dc.contributor.author McCracken, J
dc.contributor.author Muoio, DM
dc.contributor.author Narowski, R
dc.contributor.author Tune, KN
dc.coverage.spatial England
dc.date.accessioned 2017-03-01T14:09:08Z
dc.date.available 2017-03-01T14:09:08Z
dc.date.issued 2017-01-23
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/28114971
dc.identifier 10.1186/s13075-016-1215-7
dc.identifier.uri http://hdl.handle.net/10161/13703
dc.description.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.
dc.language eng
dc.relation.ispartof Arthritis Res Ther
dc.relation.isversionof 10.1186/s13075-016-1215-7
dc.subject Fibrosis
dc.subject Gene expression
dc.subject Inflammation
dc.subject Metabolomics
dc.subject Satellite cells
dc.title Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/28114971
pubs.begin-page 12
pubs.issue 1
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biomedical Engineering
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Molecular Physiology Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Medicine, Endocrinology, Metabolism, and Nutrition
pubs.organisational-group Medicine, Geriatrics
pubs.organisational-group Medicine, Rheumatology and Immunology
pubs.organisational-group Orthopaedics
pubs.organisational-group Pathology
pubs.organisational-group Pharmacology & Cancer Biology
pubs.organisational-group Pratt School of Engineering
pubs.organisational-group Sarah Stedman Nutrition & Metabolism Center
pubs.organisational-group School of Medicine
pubs.organisational-group School of Nursing
pubs.organisational-group School of Nursing - Secondary Group
pubs.publication-status Published online
pubs.volume 19
dc.identifier.eissn 1478-6362


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record