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Circulating apoptotic bodies maintain mesenchymal stem cell homeostasis and ameliorate osteopenia via transferring multiple cellular factors
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Circulating apoptotic bodies maintain mesenchymal stem cell homeostasis and ameliorate osteopenia via transferring multiple cellular factors
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Journal Article
Circulating apoptotic bodies maintain mesenchymal stem cell homeostasis and ameliorate osteopenia via transferring multiple cellular factors
2018
Overview
In the human body, 50–70 billion cells die every day, resulting in the generation of a large number of apoptotic bodies. However, the detailed biological role of apoptotic bodies in regulating tissue homeostasis remains unclear. In this study, we used Fas-deficient MRL/
lpr
and
Caspase 3
−/−
mice to show that reduction of apoptotic body formation significantly impaired the self-renewal and osteo-/adipo-genic differentiation of bone marrow mesenchymal stem cells (MSCs). Systemic infusion of exogenous apoptotic bodies rescued the MSC impairment and also ameliorated the osteopenia phenotype in MRL/
lpr
,
Caspase 3
−/−
and ovariectomized (OVX) mice. Mechanistically, we showed that MSCs were able to engulf apoptotic bodies via integrin αvβ3 and reuse apoptotic body-derived ubiquitin ligase RNF146 and miR-328-3p to inhibit Axin1 and thereby activate the Wnt/β-catenin pathway. Moreover, we used a parabiosis mouse model to reveal that apoptotic bodies participated in the circulation to regulate distant MSCs. This study identifies a previously unknown role of apoptotic bodies in maintaining MSC and bone homeostasis in both physiological and pathological contexts and implies the potential use of apoptotic bodies to treat osteoporosis.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/2
/ 13/31
/ 13/51
/ 13/89
/ 14/19
/ 64/110
/ 64/60
/ 82/80
/ Animals
/ Biomedical and Life Sciences
/ Bone Diseases, Metabolic - metabolism
/ Bone Diseases, Metabolic - pathology
/ Caspase
/ Extracellular Vesicles - metabolism
/ Female
/ Mesenchymal Stem Cells - cytology
/ Mesenchymal Stem Cells - metabolism
/ Mice
