SNX10 is required for osteoclast formation and resorption activity
SNX10 is required for osteoclast formation and resorption activity
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DOI：
10.1002/jcb.24029
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发表时间：
2012-05-01
影响因子：
4
通讯作者：
Battaglino, R. A.
中科院分区：
文献类型：
--
作者：
Zhu, C. H.;Morse, L. R.;Battaglino, R. A.
rankl刺激破骨细胞前体导致参与分化和激活过程的基因上调。在这篇报道中，我们描述了排序连接蛋白10 （snx10）的表达和功能特征。Snx10属于分类连接蛋白（SNX）家族，这是一个多样化的蛋白质群，具有共同的特征：PX结构域，参与内体的膜运输和货物分类。Snx10在体外rankl诱导的破骨细胞分化过程中被强烈上调，并在体内破骨细胞中表达。qPCR分析证实snx10在体外来源的破骨细胞以及股骨和颅骨中的表达显著增加。小鼠胚胎切片免疫组化分析显示，长骨、颅骨和发育中的牙齿中均有表达。这种表达仅限于同样表达TRAP的细胞，显示出破骨细胞的定位。共聚焦免疫荧光和亚细胞分离分析显示Snx10定位于细胞核和内质网（ER）。为了研究snx10在破骨细胞分化和功能中的可能作用，我们沉默了snx10的表达，发现snx10沉默抑制了rankl诱导的破骨细胞形成和羟基磷灰石上破骨细胞的吸收。沉默也抑制TRAP的分泌。综上所述，这些结果证实snx10在破骨细胞中表达，并且是体外破骨细胞分化和活性所必需的。由于抑制囊泡运输对破骨细胞的形成和活动至关重要，并且SNX10参与细胞内囊泡运输，因此这些研究可能会发现一个新的候选基因参与包括骨质疏松症在内的人类骨病的发展。j .细胞。中国生物医学工程学报，2012,31(2):481 - 481。(C) 2011 Wiley期刊公司
RANKL-stimulation of osteoclast precursors results in up-regulation of genes involved in the process of differentiation and activation. In this report we describe the expression and functional characterization of Sorting Nexin 10 (snx10). Snx10 belongs to the sorting nexin (SNX) family, a diverse group of proteins with a common feature: the PX domain, which is involved in membrane trafficking and cargo sorting in endosomes. Snx10 is strongly up-regulated during RANKL-induced osteoclast differentiation in vitro and expressed in osteoclasts in vivo. qPCR analysis confirmed a significant increase in the expression of snx10 in in vitro-derived osteoclasts, as well as in femur and calvaria. Immunohistochemical analysis of mouse embryo sections showed expression in long bone, calvariae, and developing teeth. The expression was limited to cells that also expressed TRAP, demonstrating osteoclastic localization. Confocal immunofluorescence and subcellular fractionation analysis revealed Snx10 localization in the nucleus and in the endoplasmic reticulum (ER). To study a possible role for snx10 in osteoclast differentiation and function we silenced snx10 expression and found that snx10 silencing inhibited RANKL-induced osteoclast formation and osteoclast resorption on hydroxyapatite. Silencing also inhibited TRAP secretion. Taken together, these results confirm that snx10 is expressed in osteoclasts and is required for osteoclast differentiation and activity in vitro. Since inhibition of vesicular trafficking is essential for osteoclast formation and activity and SNX10 is involved in intracellular vesicular trafficking, these studies may identify a new candidate gene involved in the development of human bone diseases including osteoporosis. J. Cell. Biochem. 113: 16081615, 2012. (C) 2011 Wiley Periodicals, Inc.