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      Beta-agonist drugs modulate the proliferation and differentiation of skeletal muscle cells in vitro

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          Abstract

          Essentially employed for the treatment of airway obstructions in humans, β-agonists are also known to have an anabolic effect in animals’ skeletal muscle. In vivo and in vitro studies have attested the increase in animal body mass and the hypertrophy of muscle cells following the administration of specific β-agonists. However, the contribution of β-agonists to C2C12 myoblasts growth remains obscure. We therefore aimed to investigate the impact of β1-and β2-agonist drugs on the proliferation and differentiation of skeletal muscle cells. Direct observations and cytotoxicity assay showed that clenbuterol, salbutamol, cimaterol and ractopamine enhanced muscle cell growth and viability during the proliferation stage. Structural examinations coupled to Western blot analysis indicated that salbutamol and cimaterol triggered a decrease in myotube formation. A better comprehension of the effect of β-agonists on myogenic regulatory genes in the muscle cells is crucial to establish a specific role of β-agonists in muscle development, growth, and regeneration.

          Highlights

          • Clenbuterol, salbutamol, cimaterol, and ractopamine induce molecular responses in C2C12.

          • Beta-agonists promote cell's attachment, viability, and proliferation during muscle cell proliferation stage.

          • Salbutamol and cimaterol inhibit the formation of myotubes during differentiation stage.

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          Most cited references38

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          Making muscle: skeletal myogenesis in vivo and in vitro

          Skeletal muscle is the largest tissue in the body and loss of its function or its regenerative properties results in debilitating musculoskeletal disorders. Understanding the mechanisms that drive skeletal muscle formation will not only help to unravel the molecular basis of skeletal muscle diseases, but also provide a roadmap for recapitulating skeletal myogenesis in vitro from pluripotent stem cells (PSCs). PSCs have become an important tool for probing developmental questions, while differentiated cell types allow the development of novel therapeutic strategies. In this Review, we provide a comprehensive overview of skeletal myogenesis from the earliest premyogenic progenitor stage to terminally differentiated myofibers, and discuss how this knowledge has been applied to differentiate PSCs into muscle fibers and their progenitors in vitro.
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            Building muscle: molecular regulation of myogenesis.

            The genesis of skeletal muscle during embryonic development and postnatal life serves as a paradigm for stem and progenitor cell maintenance, lineage specification, and terminal differentiation. An elaborate interplay of extrinsic and intrinsic regulatory mechanisms controls myogenesis at all stages of development. Many aspects of adult myogenesis resemble or reiterate embryonic morphogenetic episodes, and related signaling mechanisms control the genetic networks that determine cell fate during these processes. An integrative view of all aspects of myogenesis is imperative for a comprehensive understanding of muscle formation. This article provides a holistic overview of the different stages and modes of myogenesis with an emphasis on the underlying signals, molecular switches, and genetic networks.
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              Role of beta-adrenoceptor signaling in skeletal muscle: implications for muscle wasting and disease.

              The importance of beta-adrenergic signaling in the heart has been well documented, but it is only more recently that we have begun to understand the importance of this signaling pathway in skeletal muscle. There is considerable evidence regarding the stimulation of the beta-adrenergic system with beta-adrenoceptor agonists (beta-agonists). Although traditionally used for treating bronchospasm, it became apparent that some beta-agonists could increase skeletal muscle mass and decrease body fat. These so-called "repartitioning effects" proved desirable for the livestock industry trying to improve feed efficiency and meat quality. Studying beta-agonist effects on skeletal muscle has identified potential therapeutic applications for muscle wasting conditions such as sarcopenia, cancer cachexia, denervation, and neuromuscular diseases, aiming to attenuate (or potentially reverse) the muscle wasting and associated muscle weakness, and to enhance muscle growth and repair after injury. Some undesirable cardiovascular side effects of beta-agonists have so far limited their therapeutic potential. This review describes the physiological significance of beta-adrenergic signaling in skeletal muscle and examines the effects of beta-agonists on skeletal muscle structure and function. In addition, we examine the proposed beneficial effects of beta-agonist administration on skeletal muscle along with some of the less desirable cardiovascular effects. Understanding beta-adrenergic signaling in skeletal muscle is important for identifying new therapeutic targets and identifying novel approaches to attenuate the muscle wasting concomitant with many diseases.
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                Author and article information

                Contributors
                Journal
                Biochem Biophys Rep
                Biochem Biophys Rep
                Biochemistry and Biophysics Reports
                Elsevier
                2405-5808
                18 May 2021
                July 2021
                18 May 2021
                : 26
                : 101019
                Affiliations
                [a ]Department of Life Sciences, College of Biosciences and Biotechnology, National Cheng Kung University, Tainan City, 701, Taiwan, ROC
                [b ]Center for Bioscience and Biotechnology, National Cheng Kung University, Tainan City, 701, Taiwan, ROC
                [c ]Marine Biology and Cetacean Research Center, National Cheng Kung University, Tainan City, 701, Taiwan, ROC
                Author notes
                []Corresponding author. National Cheng Kung University, Department of Life Sciences, No.1 University Road, East Dist., Tainan City, 701, Taiwan, ROC. hvwang@ 123456mail.ncku.edu.tw
                [∗∗ ]Corresponding author. National Cheng Kung University, Department of Life Sciences, No.1 University Road, East Dist., Tainan City, 701, Taiwan, ROC. l58047022@ 123456ncku.edu.tw
                Article
                S2405-5808(21)00114-X 101019
                10.1016/j.bbrep.2021.101019
                8144337
                34041371
                97b2cdc2-6043-42d2-a3b9-7f5ef994de42
                © 2021 The Author(s)

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 January 2021
                : 29 April 2021
                : 7 May 2021
                Categories
                Short Communication

                agonist drugs,c2c12,proliferation,differentiation,gm, growth medium,dm, differentiation medium,myhc, myosin heavy chain,myod, myoblast determination protein 1

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