Systems biology of skeletal muscle: fiber type as an organizing principle
ABSTRACT Skeletal muscle force generation and contraction are fundamental to countless aspects of human life. The complexity of skeletal muscle physiology is simplified by fiber type classification where differences are observed from neuromuscular transmission to release of intracellular Ca(2+) from the sarcoplasmic reticulum and the resulting recruitment and cycling of cross-bridges. This review uses fiber type classification as an organizing and simplifying principle to explore the complex interactions between the major proteins involved in muscle force generation and contraction. WIREs Syst Biol Med 2012. doi: 10.1002/wsbm.1184 For further resources related to this article, please visit the WIREs website.
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ABSTRACT: Author Summary Adult skeletal muscles are classified into fast-type and slow-type, which display different resistance to muscle atrophy and metabolic protection against obesity. We identify in this manuscript a new mechanism controlling in vivo adult muscle fiber-type specification implicating a long intergenic non-coding RNA, linc-MYH. We demonstrate a three-element genetic partnership, where an enhancer under the control of the myogenic homeoprotein Six1 functions as a regulatory hub to control fibre phenotype. In this partnership, the enhancer controls positively the expression of both the adjacent fast myosin heavy chain (MYH) gene cluster and of linc-MYH. linc-MYH is present only in adult fast type skeletal myofibers and controls their phenotype by suppressing slow-type gene expression. The regulation of linc-MYH could provide a lead for new therapeutic approaches or drug development.PLoS Genetics 05/2014; 10(5):e1004386. DOI:10.1371/journal.pgen.1004386 · 8.52 Impact Factor
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ABSTRACT: Skeletal muscle is one of the most dynamic and plastic tissues of the human body. In humans, skeletal muscle comprises approximately 40 % of total body weight and contains 50-75 % of all body proteins. In general, muscle mass depends on the balance between protein synthesis and degradation and both processes are sensitive to factors such as nutritional status, hormonal balance, physical activity/exercise, and injury or disease, among others. In this review, we discuss the various domains of muscle structure and function including its cytoskeletal architecture, excitation-contraction coupling, energy metabolism, and force and power generation. We will limit the discussion to human skeletal muscle and emphasize recent scientific literature on single muscle fibers.Calcified Tissue International 10/2014; 96(3). DOI:10.1007/s00223-014-9915-y · 2.75 Impact Factor
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ABSTRACT: Skeletal muscle is a major target for tissue engineering, given its relative size in the body, fraction of cardiac output that passes through muscle beds, as well as its key role in energy metabolism and diabetes, and the need for therapies for muscle diseases such as muscular dystrophy and sarcopenia. To date, most studies with tissue-engineered skeletal muscle have utilized murine and rat cell sources. On the other hand, successful engineering of functional human muscle would enable different applications including improved methods for preclinical testing of drugs and therapies. Some of the requirements for engineering functional skeletal muscle include expression of adult forms of muscle proteins, comparable contractile forces to those produced by native muscle, and physiological force-length and force-frequency relations. This review discusses the various strategies and challenges associated with these requirements, specific applications with cultured human myoblasts, and future directions.Experimental Biology and Medicine 06/2014; 239(9). DOI:10.1177/1535370214538589 · 2.23 Impact Factor