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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
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Myostatin, also known as growth differentiation factor 8 (GDF8), is a transforming growth factor-β (TGF-β) family member that functions to limit skeletal muscle growth. Accordingly, loss-of-function mutations in myostatin result in a dramatic increase in muscle mass in humans and various animals, while its overexpression leads to severe muscle atrophy. Myostatin also exerts a significant effect on bone metabolism, as demonstrated by enhanced bone mineral density and bone regeneration in myostatin null mice. The identification of myostatin as a negative regulator of muscle and bone mass has sparked an enormous interest in developing myostatin inhibitors as therapeutic agents for treating a variety of clinical conditions associated with musculoskeletal disorders. As a result, various myostatin-targeting strategies involving antibodies, myostatin propeptides, soluble receptors, and endogenous antagonists have been generated, and many of them have progressed to clinical trials. Importantly, most myostatin inhibitors also repress the activities of other closely related TGF-β family members including GDF11, activins, and bone morphogenetic proteins (BMPs), increasing the potential for unwanted side effects, such as vascular side effects through inhibition of BMP 9/10 and bone weakness induced by follistatin through antagonizing several TGF-β family members. Therefore, a careful distinction between targets that may enhance the efficacy of an agent and those that may cause adverse effects is required with the improvement of the target specificity. In this review, we discuss the current understanding of the endogenous function of myostatin, and provide an overview of clinical trial outcomes from different myostatin inhibitors.
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참고문헌 (100)
참고문헌 신청
McPherron AC / 1997 / Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member / Nature 387:83~90
Schuelke M / 2004 / Myostatin mutation associated with gross muscle hypertrophy in a child / N Engl J Med 350:2682~2688
McPherron AC / 1997 / Double muscling in cattle due to mutations in the myostatin gene / Proc Natl Acad Sci U S A 94:12457~12461
Clop A / 2006 / A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep / Nat Genet 38:813~818
Mosher DS / 2007 / A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs / PLoS Genet 3:e79
Schuelke M / 2004 / Myostatin mutation associated with gross muscle hypertrophy in a child / N Engl J Med 350:2682~2688
McPherron AC / 1997 / Double muscling in cattle due to mutations in the myostatin gene / Proc Natl Acad Sci U S A 94:12457~12461
Clop A / 2006 / A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep / Nat Genet 38:813~818
Mosher DS / 2007 / A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs / PLoS Genet 3:e79
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