Deciphering Myostatin's Regulatory, Metabolic, and Developmental Influence in Skeletal Diseases.
Deciphering Myostatin's Regulatory, Metabolic, and Developmental Influence in Skeletal Diseases.
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DOI：
10.3389/fgene.2021.662908
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发表时间：
2021
影响因子：
3.7
通讯作者：
Phillips CL
中科院分区：
文献类型：
--
作者：
Omosule CL;Phillips CL
目前在人类和其他哺乳动物和非哺乳动物物种中的研究结果支持肌生长抑制素在肌肉的形态和功能以及细胞分化和代谢中的有效调节作用，对农业肉类生产和人类疾病具有现实意义。肌生长抑制素缺失小鼠 (mstn−/−) 表现出骨骼肌纤维增生和肥大，而绵羊和猪等大型哺乳动物中肌生长抑制素缺乏会导致肌纤维增生。肌生长抑制素的影响超出了肌肉范围，肌生长抑制素的改变存在于心肌梗塞、炎症、胰岛素抵抗、糖尿病、衰老、癌症恶病质和肌肉骨骼疾病的病理生理学中。在这篇综述中，我们探讨了肌生长抑制素在骨骼完整性和骨细胞生物学中的作用，无论是由于直接的生化信号传导还是间接的机械转导机制。在体外，肌生长抑制素以剂量依赖性方式抑制成骨细胞分化并刺激破骨细胞活性。缺乏肌生长抑制素的小鼠的破骨细胞数量也减少，皮质厚度增加，胫骨皮质组织矿物质密度增加，椎骨矿物质密度增加。此外，我们还探讨了肌生长抑制素信号传导的这些生化和生物力学影响在涉及肌肉骨骼退化的人类疾病的病理生理学中的影响。直接或通过诱饵受体对肌生长抑制素进行药理抑制已表明，在成骨不全、骨质疏松、骨关节炎、杜氏肌营养不良和糖尿病小鼠模型中，肌肉和骨骼特性得到改善。然而，最近在具有显着神经肌肉消耗和萎缩的疾病中诱导肌生长抑制素抑制的临床试验结果令人失望，这重申了肌生长抑制素抑制在人类中的复杂性和进一步探索的转化应用的必要性。
Current research findings in humans and other mammalian and non-mammalian species support the potent regulatory role of myostatin in the morphology and function of muscle as well as cellular differentiation and metabolism, with real-life implications in agricultural meat production and human disease. Myostatin null mice (mstn−/−) exhibit skeletal muscle fiber hyperplasia and hypertrophy whereas myostatin deficiency in larger mammals like sheep and pigs engender muscle fiber hyperplasia. Myostatin’s impact extends beyond muscles, with alterations in myostatin present in the pathophysiology of myocardial infarctions, inflammation, insulin resistance, diabetes, aging, cancer cachexia, and musculoskeletal disease. In this review, we explore myostatin’s role in skeletal integrity and bone cell biology either due to direct biochemical signaling or indirect mechanisms of mechanotransduction. In vitro, myostatin inhibits osteoblast differentiation and stimulates osteoclast activity in a dose-dependent manner. Mice deficient in myostatin also have decreased osteoclast numbers, increased cortical thickness, cortical tissue mineral density in the tibia, and increased vertebral bone mineral density. Further, we explore the implications of these biochemical and biomechanical influences of myostatin signaling in the pathophysiology of human disorders that involve musculoskeletal degeneration. The pharmacological inhibition of myostatin directly or via decoy receptors has revealed improvements in muscle and bone properties in mouse models of osteogenesis imperfecta, osteoporosis, osteoarthritis, Duchenne muscular dystrophy, and diabetes. However, recent disappointing clinical trial outcomes of induced myostatin inhibition in diseases with significant neuromuscular wasting and atrophy reiterate complexity and further need for exploration of the translational application of myostatin inhibition in humans.
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影响因子：
4.1
作者：
ANDERSON, JE;LENTZ, DL;JOHNSON, RB
通讯作者：
JOHNSON, RB
影响因子：
82.9
作者：
Dankbar, Berno;Fennen, Michelle;Pap, Thomas
通讯作者：
Pap, Thomas
影响因子：
6
作者：
Burch, Peter M.;Pogoryelova, Oksana;Morris, Carl
通讯作者：
Morris, Carl
影响因子：
5.8
作者：
Chew, J.;Tay, L.;Lim, W. S.
通讯作者：
Lim, W. S.
影响因子：
3.4
作者：
Attie, Kenneth M.;Borgstein, Niels G.;Sherman, Matthew L.
通讯作者：
Sherman, Matthew L.