The myostatin gene: physiology and pharmacological relevance
ABSTRACT Myostatin, which was cloned in 1997, is a potent inhibitor of skeletal muscle growth and member of the tumour growth factor-beta family. Disruption of the myostatin gene in mice induces a dramatic increase in muscle mass, caused by a combination of hypertrophy and hyperplasia. Natural mutations occurring in cattle were also associated with a significant increase in muscle mass and, recently, an inactivating myostatin mutation associated with the same phenotype was identified in humans. Studies into the molecular basis of this antimyogenic influence led to the conclusion that myostatin inhibits myoblast proliferation and differentiation through a classical tumour growth factor-beta pathway involving the activin receptor ActRIIB and Smads 2 and 3. Approaches that induce myostatin depletion or inactivation have led to a significant improvement in muscle regeneration processes, especially in degenerative diseases, through stimulation of satellite cell proliferation and differentiation. These promising data open the way to new therapeutic approaches in muscle diseases through targeting of the myostatin pathway.
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ABSTRACT: Recent advances in our understanding of the biology of muscle have led to new interest in the pharmacological treatment of muscle wasting. Loss of muscle mass and increased intramuscular fibrosis occur in both sarcopenia and muscular dystrophy. Several regulators (mammalian target of rapamycin, serum response factor, atrogin-1, myostatin, etc.) seem to modulate protein synthesis and degradation or transcription of muscle-specific genes during both sarcopenia and muscular dystrophy. This review provides an overview of the adaptive changes in several regulators of muscle mass in both sarcopenia and muscular dystrophy.Frontiers in Aging Neuroscience 08/2014; 6:230. DOI:10.3389/fnagi.2014.00230 · 2.84 Impact FactorThis article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.
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ABSTRACT: The complexity of cell interactions with their microenvironment and their ability to communicate at the autocrine, paracrine, and endocrine levels has gradually but significantly evolved in the last three decades. The musculoskeletal system has been historically recognized to be governed by a relationship of proximity and function, chiefly dictated by mechanical forces and the work of gravity itself. In this review article, we first provide a historical overview of the biomechanical theory of bone–muscle interactions. Next, we expand to detail the significant evolution in our understanding of the function of bones and muscles as secretory organs. Then, we review and discuss new evidence in support of a biochemical interaction between these two tissues. We then propose that these two models of interaction are complementary and intertwined providing for a new frontier for the investigation of how bone–muscle cross talk could be fully explored for the targeting of new therapies for musculoskeletal diseases, particularly the twin conditions of aging, osteoporosis and sarcopenia. In the last section, we explore the bone–muscle cross talk in the context of their interactions with other tissues and the global impact of these multi-tissue interactions on chronic diseases.Clinical Reviews in Bone and Mineral Metabolism 06/2013; 12(2):77-85. DOI:10.1007/s12018-013-9152-3