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Rheumatology International

, Volume 38, Issue 6, pp 1031–1041 | Cite as

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

  • Rasmus Jentoft Boutrup
  • Jean Farup
  • Kristian Vissing
  • Michael Kjaer
  • Ulla Ramer Mikkelsen
Observational Research

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.

Keywords

Cross-sectional studies Interleukin-6 Rheumatoid arthritis Skeletal muscle Stem cells Tumor necrosis factor-alpha 

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

Notes

Acknowledgements

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

Author 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.

Funding

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

Compliance with ethical standards

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Section for Sport Science, Department of Public HealthAarhus UniversityAarhus CDenmark
  2. 2.Research Laboratory for Biochemical Pathology, Department for Clinical MedicineAarhus UniversityAarhusDenmark
  3. 3.Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Center Healthy Aging, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark

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