Research Article: Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

Date Published: March 30, 2018

Publisher: John Wiley and Sons Inc.

Author(s): Yong Xie, Yanpan Gao, Licheng Zhang, Yanyu Chen, Wei Ge, Peifu Tang.

http://doi.org/10.1111/acel.12758

Abstract

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.

Partial Text

Osteoporosis and osteopenia (low bone mass) are associated with a high risk of fractures, with approximately 25,000 osteoporotic fractures occurring daily, an incidence that is greater than the combined incidence of heart attacks and strokes worldwide. Thus, osteoporosis and osteopenia represent an important global public health issue that is associated with a persistent decrease in the quality of life of affected individuals, especially in the elderly (Barker et al., 2016). These bone disorders are predominantly caused by the failure of bone remodeling, which involves renewal of aged bone and repair of skeletal microdamage through processes that include enhanced osteoclast activity or decreased bone formation from osteoblast lineage cells (Henriksen, Karsdal & Martin, 2014).

Previous studies have demonstrated the multiple roles of bone‐derived exosomes in bone remodeling; however, none have been reported describing proteomics analysis of the differences between SDEs from aged patients with low bone density and normal volunteers. In the present study, we discovered that the SDEs from osteoporosis patients inhibited osteoblastic bone matrix mineralization and promoted osteoclast differentiation. In contrast, SDEs from osteopenia patients enhanced both osteoblast function and osteoclast activation, leading to a compensatory increase in bone remodeling. A comprehensive analysis of the changes in proteins in these exosomes was conducted by TMT‐based MS, which has the advantages of maximum protein coverage and precise quantification. The DEPs identified were involved in different processes and functions intrinsic to bone, including mechanosensation, inflammation, and cell senescence, which are the apparent protagonists in bone remodeling.

The authors report no conflict of interest relevant to this article.

P.T. and W.G. designed the research. Y.X., Y.G., and L.Z. performed the research. Y.X., Y.G., and Y.C. analyzed the data. L.Z. provided serum samples and reagents. Y.X. and Y.G. wrote the manuscript.

 

Source:

http://doi.org/10.1111/acel.12758

 

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