Circulating apoptotic bodies maintain mesenchymal stem cell homeostasis and ameliorate osteopenia via transferring multiple cellular factors

Cell Research
Dawei LiuS Shi

Abstract

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.

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Citations

Sep 2, 2020·Biochemical Society Transactions·Thanh Kha PhanIvan Ka Ho Poon
Jan 27, 2019·Apoptosis : an International Journal on Programmed Cell Death·Lanzhou Jiang, Ivan K H Poon
Jun 26, 2020·Cardiovascular Research·Lucio Barile, Tomasz J Guzik
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Jun 2, 2020·Frontiers in Bioengineering and Biotechnology·Tingting YuBing Han
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Methods Mentioned

BETA
flow cytometry
ubiquitination
PCR
transfection

Software Mentioned

RT 2 Profiler
DIANA
Amira
Image J
Image
Ingenuity Pathway Analysis ( IPA )
Targetscan

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