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Annexin-enriched osteoblast-derived vesicles act as an extracellular site of mineral nucleation within developing stem cell cultures

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posted on 31.10.2017, 11:37 authored by Owen DaviesOwen Davies, Sophie C. Cox, R.L. Williams, D. Tsaroucha, R.M. Dorrepaal, Mark LewisMark Lewis, L.M. Grover
The application of extracellular vesicles (EVs) as natural delivery vehicles capable of enhancing tissue regeneration could represent an exciting new phase in medicine. We sought to define the capacity of EVs derived from mineralising osteoblasts (MO-EVs) to induce mineralisation in mesenchymal stem cell (MSC) cultures and delineate the underlying biochemical mechanisms involved. Strikingly, we show that the addition of MO-EVs to MSC cultures significantly (P < 0.05) enhanced the expression of alkaline phosphatase, as well as the rate and volume of mineralisation beyond the current gold-standard, BMP-2. Intriguingly, these effects were only observed in the presence of an exogenous phosphate source. EVs derived from non-mineralising osteoblasts (NMO-EVs) were not found to enhance mineralisation beyond the control. Comparative label-free LC-MS/MS profiling of EVs indicated that enhanced mineralisation could be attributed to the delivery of bridging collagens, primarily associated with osteoblast communication, and other non-collagenous proteins to the developing extracellular matrix. In particular, EV-associated annexin calcium channelling proteins, which form a nucleational core with the phospholipid-rich membrane and support the formation of a pre-apatitic mineral phase, which was identified using infrared spectroscopy. These findings support the role of EVs as early sites of mineral nucleation and demonstrate their value for promoting hard tissue regeneration.

Funding

The work was directly funded by an EPSRC E-TERM Landscape fellowship personally awarded to Dr. Owen Davies. R.M. Dorrepaal was funded by the European Research Council (ERC) under the starting grant programme ERC-2013-StG call—Proposal No. 335508—BioWater.

History

School

  • Sport, Exercise and Health Sciences

Published in

SCIENTIFIC REPORTS

Volume

7

Citation

DAVIES, O.G. ...et al., 2017. Annexin-enriched osteoblast-derived vesicles act as an extracellular site of mineral nucleation within developing stem cell cultures. Scientific Reports, 7: 12639.

Publisher

© the Authors. Published by the Nature Publishing Group

Version

VoR (Version of Record)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/ by/4.0/

Acceptance date

19/09/2017

Publication date

2017-10-03

Copyright date

2017

Notes

This is an Open Access Article. It is published by Nature under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/

ISSN

2045-2322

Language

en

Article number

12639