Background/Purpose: Satellite cells are myogenic stem cells that are essential for myofiber repair, growth and homeostasis in postnatal life. A decline in satellite cell performance has been previously linked with age-associated loss of muscle mass and function; and may also underlie skeletal muscle dysfunction in patients with polymyositis (PM) and dermatomyositis (DM). Successful regeneration of skeletal muscle relies not only on satellite cells, but also on a fine balance between pro- and anti-inflammatory factors. We hypothesize that in disease processes such as PM/ DM where chronic inflammation ensues, dysregulated inflammatory responses could lead to inhibition of effective muscle repair and remodeling by inhibiting satellite cell activation and myofiber maturation, and promoting scar tissue formation.

Methods: Skeletal muscle biopsy samples were obtained from 12 treatment refractory DM/PM patients; and 12 generally healthy volunteers who served as age, sex and BMI matched controls. Control biopsy samples were obtained from a skeletal muscle biorepository maintained by the University of Kentucky. Markers of myogenesis, M1/M2 macrophage phenotypes, and pro- and anti-inflammatory markers were assessed by RT-PCR. The data are represented as fold-change compared to controls. Mean values were compared between controls and PM/DM using two sample t-tests. Spearman rank correlations were used to examine the relationships of markers of myogenesis and immunity with selected disease activity/ damage measures among PM/DM subjects.

Results: In Figure1, gene expression of Pax7, a marker of quiescent satellite cells, and embryonic myosin heavy chain (MyH3), a marker of regenerative myofiber formation, are significantly upregulated, while gene expression of MyoD1 and myogenin, markers of activated satellite cells, are either significantly downregulated or not significantly different between PM/DM and controls. Gene expression of pro- (IL6, MCP1) and anti-inflammatory (IL1 Ra, IL4, TGFB and TSP1) markers, as well as both M1 (CD68/11b) and M2 (CD68/206) macrophage markers are significantly upregulated in PM/DM versus controls. Among the markers of myogenesis, only myogenin significantly correlated with MMT-8 muscle testing (r=-0.68, p=0.022), MDAAT muscle disease activity VAS (r=0.82., p=0.002) and serum CK level (r=0.87, p<0.001).

Conclusion: These findings suggest that in PM/DM, the pool of quiescent satellite cells is maintained; regenerative myofiber formation occurs to a certain extent; while activation and terminal differentiation of satellite cells is inhibited. It is interesting to note that gene expression of MyH3 did not correlate significantly with muscle strength. Further studies are needed to determine if embryonic-to-adult myosin heavy chain switch occurs normally in patients with PM/DM, and its effect on functional restoration of myofibers.