Moonlighting osteoclasts as undertakers of apoptotic cells
Moonlighting osteoclasts as undertakers of apoptotic cells
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DOI：
10.3109/08916934.2012.719950
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发表时间：
2012-12-01
期刊：
影响因子：
3.5
通讯作者：
Lauber, Kirsten
中科院分区：
文献类型：
--
作者：
Harre, Ulrike;Keppeler, Hildegard;Lauber, Kirsten
凋亡细胞的快速清除，通常被称为红细胞增多症，对于维持组织稳态和预防自身免疫至关重要。凋亡细胞清除的常见模型涉及凋亡细胞上释放的“找到我”和暴露的“吃我”信号的系统，其通过巨噬细胞或树突细胞（DC）上的匹配受体（称为吞噬突触）检测和识别。破骨细胞与这些专职单核吞噬细胞共享单核细胞谱系，因此提出了一个问题，除了骨吸收，破骨细胞是否可以作为凋亡细胞的清道夫。我们的qPCR数据清楚地表明，破骨细胞表达死亡细胞清除所需的大部分基因，其mRNA水平与M1-巨噬细胞、M2-巨噬细胞或DC中观察到的相似或甚至更高。我们的显微镜分析表明，破骨细胞事实上可以结合和/或吞噬凋亡细胞在一个基本上血清不依赖的方式。结合我们关于各自mRNA丰度的数据，这些结果鉴定了玻连蛋白受体（整合素α（nu）β（3））/乳脂球蛋白-EGF因子8蛋白（MFG-E8）轴，清道夫受体（CD 36，CD 68和A类巨噬细胞清道夫受体（SR-A）），补体/补体受体轴，Mer/Tyro 3/蛋白S轴，和磷脂酰丝氨酸（PS）受体脑特异性血管生成抑制剂1（BAI 1）作为最有希望的候选者参与破骨细胞介导的红细胞增多症。
Rapid clearance of apoptotic cells, frequently referred to as efferocytosis, is crucial for the maintenance of tissue homeostasis and the prevention of autoimmunity. The common model of apoptotic cell clearance involves a system of released "Find me" and exposed "Eat me" signals on apoptotic cells, detected and recognized by matching receptors on macrophages or dendritic cells (DC), referred to as the phagocytic synapse. Osteoclasts share the monocyte lineage with these professional mononuclear phagocytes, thus raising the question if, in addition to bone resorption, osteoclasts can act as scavengers for apoptotic cells. Our qPCR data clearly show that osteoclasts express most of the genes required for dying cell clearance at mRNA levels similar to or even higher than those observed in M1-macrophages, M2-macrophages or DC. Our microscopical analyses reveal that osteoclasts in fact can bind and/or engulf apoptotic cells in an essentially serum-independent fashion. Together with our data on the abundance of the respective mRNAs, these results identify the vitronectin receptor (integrin alpha(nu)beta(3))/milk fat globule-EGF factor 8 protein (MFG-E8) axis, the scavenger receptors (CD36, CD68 and class A macrophage scavenger receptor (SR-A)), the complement/complement receptor axis, the Mer/Tyro3/Protein S axis, and the phosphatidylserine (PS) receptor brain-specific angiogenesis inhibitor 1 (BAI1) as the most promising candidates to be involved in osteoclast-mediated efferocytosis.