Volume 28, No 9, Sep 2018

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 28 Issue 9, September 2018: 918-933

ORIGINAL ARTICLES

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

Dawei Liu ^1,2,3, Xiaoxing Kou ^1,2, Chider Chen ², Shiyu Liu ⁴, Yao Liu ², Wenjing Yu ², Tingting Yu ^1,2, Ruili Yang ^1,2, Runci Wang ²,Yanheng Zhou ¹ and Songtao Shi ^2,3

¹ Department of Orthodontics, Peking University School & Hospital of Stomatology, #22 Zhongguancun South Avenue, Beijing 100081, China; ² Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA; ³ Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA and 4School of Stomatology, Fourth Military Medical University, Xi’an, Shanxi 710032, China Correspondence: Songtao Shi (songtaos@upenn.edu)These authors contributed equally: Dawei Liu, Xiaoxing Kou

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.

https://doi.org/10.1038/s41422-018-0070-2

FULL TEXT | PDF

Browse 713