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

TY - JOUR

T1 - Skeletal muscle stem cell characteristics and myonuclei content in patients with rheumatoid arthritis

T2 - a cross-sectional study

AU - Boutrup, Rasmus Jentoft

AU - Farup, Jean

AU - Vissing, Kristian

AU - Kjaer, Michael

AU - Mikkelsen, Ulla Ramer

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

KW - Arthritis, Rheumatoid/pathology

KW - Cross-Sectional Studies

KW - Denmark

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Muscle, Skeletal/cytology

KW - Satellite Cells, Skeletal Muscle/pathology

U2 - 10.1007/s00296-018-4028-y

DO - 10.1007/s00296-018-4028-y

M3 - Journal article

C2 - 29651539

SN - 0172-8172

VL - 38

SP - 1031

EP - 1041

JO - Rheumatology International

JF - Rheumatology International

IS - 6

ER -