Jin-Yu Liu, Jie-Xi Liu, Rang Li, Zi-Qi Zhang, Xiao-Hui Zhang, Shu-Juan Xing, Bing-Dong Sui, Fang Jin, Bo Ma, Chen-Xi Zheng
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引用次数: 0
摘要
AMP 激活蛋白激酶(AMPK)是一种重要的调节激酶,它能监测能量水平,在低营养、低能量状态下保存 ATP 并促进合成。它的敏感性将微环境变化与细胞反应联系起来。作为主要的支撑结构和内分泌器官,骨骼的维护和修复与微环境密切相关。虽然一系列研究探讨了特定微环境对骨骼的影响,但还缺乏全面评估微环境与骨细胞之间相互作用的角度,尤其是骨髓间充质干细胞(BMMSCs)介导成骨系的分化。值得注意的是,越来越多的证据表明,AMPK可能是骨髓间充质干细胞和微环境因素之间的枢纽,从而为我们理解干细胞和骨骼的生物学和病理生理学提供了一个新的视角。在这篇综述中,我们强调了AMPK通过ATP、炎症、活性氧(ROS)、钙和葡萄糖在骨微环境调节中的关键作用,尤其是在BMMSCs中。我们进一步探讨了 AMPK 激活药物在骨关节炎和骨质疏松症中的应用。此外,在AMPK的基础上,我们阐明了一种观点,有助于全面理解微环境与骨稳态之间的动态关系,为干细胞生物学的前瞻性研究和骨病治疗提供了宝贵的见解。
AMPK, a hub for the microenvironmental regulation of bone homeostasis and diseases.
AMP-activated protein kinase (AMPK), a crucial regulatory kinase, monitors energy levels, conserving ATP and boosting synthesis in low-nutrition, low-energy states. Its sensitivity links microenvironmental changes to cellular responses. As the primary support structure and endocrine organ, the maintenance, and repair of bones are closely associated with the microenvironment. While a series of studies have explored the effects of specific microenvironments on bone, there is lack of angles to comprehensively evaluate the interactions between microenvironment and bone cells, especially for bone marrow mesenchymal stem cells (BMMSCs) which mediate the differentiation of osteogenic lineage. It is noteworthy that accumulating evidence has indicated that AMPK may serve as a hub between BMMSCs and microenvironment factors, thus providing a new perspective for us to understand the biology and pathophysiology of stem cells and bone. In this review, we emphasize AMPK's pivotal role in bone microenvironment modulation via ATP, inflammation, reactive oxygen species (ROS), calcium, and glucose, particularly in BMMSCs. We further explore the use of AMPK-activating drugs in the context of osteoarthritis and osteoporosis. Moreover, building upon the foundation of AMPK, we elucidate a viewpoint that facilitates a comprehensive understanding of the dynamic relationship between the microenvironment and bone homeostasis, offering valuable insights for prospective investigations into stem cell biology and the treatment of bone diseases.
期刊介绍:
The Journal of Cellular Physiology publishes reports of high biological significance in areas of eukaryotic cell biology and physiology, focusing on those articles that adopt a molecular mechanistic approach to investigate cell structure and function. There is appreciation for the application of cellular, biochemical, molecular and in vivo genetic approaches, as well as the power of genomics, proteomics, bioinformatics and systems biology. In particular, the Journal encourages submission of high-interest papers investigating the genetic and epigenetic regulation of proliferation and phenotype as well as cell fate and lineage commitment by growth factors, cytokines and their cognate receptors and signal transduction pathways that influence the expression, integration and activities of these physiological mediators. Similarly, the Journal encourages submission of manuscripts exploring the regulation of growth and differentiation by cell adhesion molecules in addition to the interplay between these processes and those induced by growth factors and cytokines. Studies on the genes and processes that regulate cell cycle progression and phase transition in eukaryotic cells, and the mechanisms that determine whether cells enter quiescence, proliferate or undergo apoptosis are also welcomed. Submission of papers that address contributions of the extracellular matrix to cellular phenotypes and physiological control as well as regulatory mechanisms governing fertilization, embryogenesis, gametogenesis, cell fate, lineage commitment, differentiation, development and dynamic parameters of cell motility are encouraged. Finally, the investigation of stem cells and changes that differentiate cancer cells from normal cells including studies on the properties and functions of oncogenes and tumor suppressor genes will remain as one of the major interests of the Journal.