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

Huffman, Kim M

Jessee, Ryan

Andonian, Brian

Davis, Brittany N

Narowski, Rachel

Huebner, Janet L

Kraus, Virginia B

McCracken, Julie

Gilmore, Brian F

Tune, K Noelle

Campbell, Milton

Koves, Timothy R

Muoio, Deborah M

Hubal, Monica J

Kraus, William E

England

2017-03-01T14:09:08Z

2017-03-01T14:09:08Z

2017-01-23

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.

https://www.ncbi.nlm.nih.gov/pubmed/28114971

10.1186/s13075-016-1215-7

1478-6362

https://hdl.handle.net/10161/13703

eng

Springer Science and Business Media LLC

Arthritis Res Ther

10.1186/s13075-016-1215-7

Fibrosis

Gene expression

Inflammation

Metabolomics

Satellite cells

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

Journal article

Andonian, Brian|0000-0003-1847-0660

Kraus, Virginia B|0000-0001-8173-8258

Koves, Timothy R|0000-0001-8763-5866

Muoio, Deborah M|0000-0003-3760-9277

Kraus, William E|0000-0003-1930-9684

https://www.ncbi.nlm.nih.gov/pubmed/28114971

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Basic Science Departments

Biomedical Engineering

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Molecular Physiology Institute

Institutes and Centers

Medicine

Medicine, Cardiology

Medicine, Endocrinology, Metabolism, and Nutrition

Medicine, Geriatrics

Medicine, Rheumatology and Immunology

Orthopaedics

Pathology

Pharmacology & Cancer Biology

Pratt School of Engineering

Sarah Stedman Nutrition & Metabolism Center

School of Medicine

School of Nursing

School of Nursing - Secondary Group

Published online

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