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Skeletal muscle stem cell characteristics and myonuclei content in patients with rheumatoid arthritis: a cross-sectional study

  • Observational Research
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Abstract

To investigate satellite cells (SCs) and myonuclei characteristics in patients with rheumatoid arthritis (RA). Resting biopsies from m. vastus lateralis were obtained from thirteen RA patients and thirteen matched healthy controls (CON). Muscle biopsies were immunohistochemically stained and analyzed for fiber type specific content of SCs (Pax7+), proliferating SCs (Pax7+/MyoD+) and differentiating SCs (myogenin+). Furthermore, we quantified fiber type specific content of myonuclei and myofiber cross-sectional area (CSA). Finally, newly formed/regenerating fibers expressing neonatal MHC (nMHC+) were determined. The fiber type specific number of SCs did not differ between RA patients and CON, nor did the content of proliferating or differentiating SCs. In contrast, the content of myonuclei per fiber was higher in RA patients than CON for both type I (2.01 ± 0.41 vs. 1.42 ± 0.40 myonuclei/fiber, p < 0.01) and type II fibers (2.01 ± 0.41 vs. 1.37 ± 0.32 myonuclei/fiber, p < 0.01). No differences were observed in fiber composition, fiber type specific CSA or content of nMHC+ fibers. Our results indicate an increased propensity for myogenic differentiation of SC leading to an elevated myonuclear content in the skeletal muscle of RA patients. It is hypothesized that this could be a compensatory regulatory response related to the chronic inflammation in these patients.

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Abbreviations

CON:

Control

CSA:

Cross-sectional area

IL-6:

Interleukin-6

JAK2:

Janus kinase 2

LGI:

Low-grade inflammation

RA:

Rheumatoid arthritis

SC:

Satellite cell

STAT3:

Signal transducer and activator of transcription 3

SOCS3:

Suppressor of cytokine signaling 3

TNF-α:

Tumor necrosis factor-alpha

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Acknowledgements

We would like to thank all the participants in the study and Simon Riis for analyzing the MRI data.

Funding

The study was funded by The Danish Medical Research Council (10-094021) and the Nordea Foundation (Center for Healthy Aging).

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Authors and Affiliations

  1. Section for Sport Science, Department of Public Health, Aarhus University, Dalgas Avenue 6, 8000, Aarhus C, Denmark

    Rasmus Jentoft Boutrup, Kristian Vissing & Ulla Ramer Mikkelsen

  2. Research Laboratory for Biochemical Pathology, Department for Clinical Medicine, Aarhus University, Aarhus, Denmark

    Jean Farup

  3. Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Center Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Michael Kjaer & Ulla Ramer Mikkelsen

Authors
  1. Rasmus Jentoft Boutrup
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  2. Jean Farup
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  4. Michael Kjaer
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  5. Ulla Ramer Mikkelsen
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Contributions

Conceived the study: RJB, JF, MK, URM. Participated in the study design: RJB, JF, MK, URM. Carried out the study: RJB, JF, KV, URM. Data acquisition: RJB, JF. Data analyses and interpretation: RJB, JF, KV, URM. Wrote the manuscript: RJB, JF, KV, URM. All authors have read and approved the final version of the manuscript.

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Correspondence to Rasmus Jentoft Boutrup.

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Conflict of interest

All authors declare that they have no conflict of interest.

Ethics approval

The study was approved by The Research Ethics Committees of the Capital Region of Denmark (H-4-2011-028) and conformed to the Declaration of Helsinki.

Informed consent

Written informed consent was obtained from all subjects before participation.

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Boutrup, R.J., Farup, J., Vissing, K. et al. Skeletal muscle stem cell characteristics and myonuclei content in patients with rheumatoid arthritis: a cross-sectional study. Rheumatol Int 38, 1031–1041 (2018). https://doi.org/10.1007/s00296-018-4028-y

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