前列腺素E2:从临床应用到其在骨-肌肉相互作用及肌源性分化中的潜在作用

Prostaglandin E2: from clinical applications to its potential role in bone- muscle crosstalk and myogenic differentiation.

作者信息

Mo Chenglin, Romero-Suarez Sandra, Bonewald Lynda, Johnson Mark, Brotto Marco

机构信息

University of Missouri-Kansas City, Muscle Biology Research Group-MUBIG, School of Nursing, Kansas City, MO, 64108, USA.

出版信息

Recent Pat Biotechnol. 2012 Dec;6(3):223-9. doi: 10.2174/1872208311206030223.

Abstract

Prostaglandin E(2) (PGE(2)), a prostanoid synthesized from arachidonic acid via the cyclooxygenase pathway, is a modulator of physiological responses including inflammation, fever, and muscle regeneration. Several patents have been filed that are related to PGE(2), one of them being directly related to skeletal muscles. In this report, we first summarize the key patents describing inventions for the utilization of PGE(2) for either diagnostic or therapeutic purposes, including skeletal muscle. In the second part of our work we present new and exciting data that demonstrates that PGE(2) accelerates skeletal muscle myogenic differentiation. Our discovery resulted from our recent and novel concept of bone-muscle crosstalk. Bone and muscle are anatomically intimate endocrine organs and we aimed to determine whether this anatomical intimacy also translates into a biochemical communication from bone cells to muscle cells at the in vitro level. The effects of MLOY4 osteocyte-like cell conditioned medium (CM) and three osteocyte-secreted factors, PGE(2), sclerostin and monocyte chemotactic protein (MCP-3), on C2C12 myogenic differentiation were evaluated using morphological analyses, a customized 96-gene PCR array, and measurements of intracellular calcium levels. MLO-Y4 CM and PGE(2), but not sclerostin and MCP-3, induced acceleration of myogenesis of C2C12 myoblasts that was linked with significant modifications in intracellular calcium homeostasis. This finding should further stimulate the pursuit of new patents to explore the use of PGE(2) and the new concept of bone-muscle crosstalk for the development and application of inventions designed to treat muscle diseases characterized by enhanced muscle wasting, such as sarcopenia.

摘要

前列腺素E(2)(PGE(2))是一种通过环氧化酶途径由花生四烯酸合成的类前列腺素,是包括炎症、发热和肌肉再生在内的生理反应的调节剂。已经提交了几项与PGE(2)相关的专利,其中一项与骨骼肌直接相关。在本报告中,我们首先总结了描述将PGE(2)用于诊断或治疗目的(包括骨骼肌)的发明的关键专利。在我们工作的第二部分,我们展示了新的、令人兴奋的数据,这些数据表明PGE(2)加速骨骼肌成肌分化。我们的发现源于我们最近提出的骨-肌肉相互作用的新概念。骨和肌肉是解剖学上紧密相连的内分泌器官,我们旨在确定这种解剖学上的紧密联系是否也能在体外水平上转化为从骨细胞到肌肉细胞的生化通讯。使用形态学分析、定制的96基因PCR阵列和细胞内钙水平测量,评估了MLOY4骨细胞样细胞条件培养基(CM)以及三种骨细胞分泌因子PGE(2)、硬化蛋白和单核细胞趋化蛋白(MCP-3)对C2C12成肌分化的影响。MLO-Y4 CM和PGE(2),而不是硬化蛋白和MCP-3,诱导C2C12成肌细胞的成肌作用加速,这与细胞内钙稳态的显著改变有关。这一发现应该会进一步刺激人们寻求新的专利,以探索PGE(2)的用途以及骨-肌肉相互作用的新概念,用于开发和应用旨在治疗以肌肉萎缩增强为特征的肌肉疾病(如肌肉减少症)的发明。

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