The Influence of Passive Stretch and NF-κB Inhibitors on the Morphology of Dystrophic Muscle Fibers

Department of Physiology, Kirksville College of Osteopathic Medicine, AT Still University, Kirksville, Missouri.
The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology (Impact Factor: 1.54). 01/2011; 294(1):132-44. DOI: 10.1002/ar.21294
Source: PubMed


The triangularis sterni (TS) is an expiratory muscle that is passively stretched during inspiration. The magnitude of passive stretch depends upon the location of individual fibers within the TS muscle, with fibers located more caudally being stretched ∼ 5% to 10% more than fibers in the cephalad region. In the mdx mouse model for muscular dystrophy, the TS exhibits severe pathological alterations that are ameliorated by treatment with inhibitors of the NF-κB pathway. The purpose of this study was to assess the influence of passive stretch in vivo on fiber morphology in nondystrophic and mdx TS muscles, and the morphological benefits of treating mdx mice with two distinct NF-κB inhibitors, pyrrolidine dithiocarbamate (PDTC), and ursodeoxycholic acid (UDCA). Transmission electron microscopy revealed Z-line streaming, hypercontraction, and disassociation of the plasma membrane from the basal lamina in mdx fibers. In both nondystrophic and mdx TS muscles, fiber density was larger in more caudal regions. In comparison with nondystrophic TS, fibers in the mdx TS exhibited substantial reductions in diameter throughout all regions. In vivo treatment with either PDTC or UDCA tended to increase fiber diameter in the middle and decrease fiber diameter in the caudal TS, while reducing centronucleation in the middle region. These results suggest that passive stretch induces hypercontraction and plasma membrane abnormalities in dystrophic muscle, and that differences in the magnitude of passive stretch may influence fiber morphology and the actions of NF-κB inhibitors on dystrophic morphology.

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Available from: Cgeorge Carlson, Sep 14, 2015
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    • "an enhanced susceptibility to denervation - induced atrophy ( Cai et al . , 2004 ; Mourkioti et al . , 2006 ) . This influence of the pathway in mature differentiated fibers is supported by results showing that in vivo treatment of mdx mice with NF - kB inhibitors increases fiber diameter in the middle region of the severely dystrophic TS muscle ( Siegel et al . , 2011 ) . In summary , developing muscle appears to exhibit four distinct developmental stages with respect to NF - kB signaling ."
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