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破骨细胞的代谢特性。

Metabolic properties of the osteoclast.

机构信息

Department of Cell & Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.

Department of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.

出版信息

Bone. 2018 Oct;115:25-30. doi: 10.1016/j.bone.2017.12.021. Epub 2017 Dec 21.

Abstract

Osteoclasts are defined as cells capable of excavating 3-dimensional resorption pits in bone and other mineralised tissues. They are derived from the differentiation/fusion of promonocytic precursors, and are usually large, multinucleated cells. In common with other cells from this myeloid lineage such as macrophages and dendritic cells, they are adapted to function in hypoxic, acidic environments. The process of bone resorption is rapid and is presumably highly energy-intensive, since osteoclasts must actively extrude protons to dissolve hydroxyapatite mineral, whilst secreting cathepsin K to degrade collagen, as well as maintaining a high degree of motility. Osteoclasts are well known to contain abundant mitochondria but they are also able to rely on glycolytic (anaerobic) metabolism to generate the ATP needed to power their activity. Their primary extracellular energy source appears to be glucose. Excessive accumulation of mitochondrial reactive oxygen species in osteoclasts during extended periods of high activity in oxygen-poor environments may promote apoptosis and help to limit bone resorption - a trajectory that could be termed "live fast, die young". In general, however, the metabolism of osteoclasts remains a poorly-investigated area, not least because of the technical challenges of studying actively resorbing cells in appropriate conditions.

摘要

破骨细胞被定义为能够在骨骼和其他矿化组织中挖掘三维吸收陷窝的细胞。它们来源于单核细胞前体的分化/融合,通常是大的多核细胞。与巨噬细胞和树突状细胞等其他来自髓样谱系的细胞一样,它们适应于在低氧、酸性环境中发挥功能。骨吸收的过程是迅速的,据推测高度依赖能量,因为破骨细胞必须主动排出质子来溶解羟基磷灰石矿物质,同时分泌组织蛋白酶 K 来降解胶原蛋白,以及保持高度的运动性。众所周知,破骨细胞含有丰富的线粒体,但它们也能够依赖糖酵解(无氧)代谢来产生活动所需的 ATP。它们的主要细胞外能量来源似乎是葡萄糖。在低氧环境中长时间高活性期间,破骨细胞中线粒体活性氧的过度积累可能会促进细胞凋亡,并有助于限制骨吸收——这一过程可以被称为“快速生长,早逝”。然而,一般来说,破骨细胞的代谢仍然是一个研究不足的领域,这主要是因为在适当条件下研究活跃吸收细胞存在技术挑战。

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