Involvement of serum-derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone-related proteins.

Involvement of serum-derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone-related proteins.
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DOI:
10.1111/acel.12758
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发表时间:
2018-06
期刊:
影响因子:
7.8
通讯作者:
Tang P
Tang P
中科院分区:
生物学1区
文献类型:
--
作者:
Xie Y;Gao Y;Zhang L;Chen Y;Ge W;Tang P

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外切体由各种类型的细胞分泌到血液中。在骨重建失败时,这些细胞外小泡参与外体蛋白对成骨细胞或破骨细胞调节网络的贡献,从而导致与年龄相关的骨丢失。然而,老年低骨密度患者血清来源的外切体(SDE)的分子变化及其在骨重建中的作用仍未完全阐明。我们提供了从老年骨质疏松症/骨量减少症患者和正常志愿者血清中纯化的外切体的定量蛋白质组学分析;这些数据可以通过标识为PXD006463的蛋白质组XChange获得。总体而言,鉴定了1,371种蛋白质,在ExoCarta蛋白质中重叠了1,160个基因ID。生物信息学分析和体外研究表明,骨质疏松患者SDE中蛋白质的变化不仅参与了抑制整合素介导的成骨细胞的机械感受和激活,而且还触发了破骨细胞的分化和吸收。相比之下,骨量减少患者的SDE的主要变化促进了破骨细胞的激活和新骨量的形成,这可能导致骨重建的代偿性升高。而老年正常志愿者的SDE可能通过促进骨细胞的黏附和抑制衰老相关的氧化应激而对骨骼健康起到保护作用。这些信息将有助于阐明SDE的病理生理功能,并有助于老年性骨质疏松症的诊断和治疗。
Exosomes are secreted into the blood by various types of cells. These extracellular vesicles are involved in the contribution of exosomal proteins to osteoblastic or osteoclastic regulatory networks during the failure of bone remodeling, which results in age‐related bone loss. However, the molecular changes in serum‐derived exosomes (SDEs) from aged patients with low bone density and their functions in bone remodeling remain to be fully elucidated. We present a quantitative proteomics analysis of exosomes purified from the serum of the elderly patients with osteoporosis/osteopenia and normal volunteers; these data are available via Proteome Xchange with the identifier PXD006463. Overall, 1,371 proteins were identified with an overlap of 1,160 Gene IDs among the ExoCarta proteins. Bioinformatics analysis and in vitro studies suggested that protein changes in SDEs of osteoporosis patients are not only involved in suppressing the integrin‐mediated mechanosensation and activation of osteoblastic cells, but also trigger the differentiation and resorption of osteoclasts. In contrast, the main changes in SDEs of osteopenia patients facilitated both activation of osteoclasts and formation of new bone mass, which could result in a compensatory elevation in bone remodeling. While the SDEs from aged normal volunteers might play a protective role in bone health through facilitating adhesion of bone cells and suppressing aging‐associated oxidative stress. This information will be helpful in elucidating the pathophysiological functions of SDEs and aid in the development of senile osteoporosis diagnostics and therapeutics.
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