Royal College of Surgeons in Ireland
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Mechanically activated mesenchymal-derived bone cells drive vessel formation via an extracellular vesicle mediated mechanism.pdf (2.16 MB)

Mechanically activated mesenchymal-derived bone cells drive vessel formation via an extracellular vesicle mediated mechanism

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posted on 2023-09-12, 09:32 authored by N. Shen, M. Maggio, I. Woods, M.C. Lowry, R. Almasri, Cansu GorgunCansu Gorgun, K.F. Eichholz, E. Stavenschi, K. Hokamp, F.M. Roche, L. O’Driscoll, D.A. Hoey

Blood vessel formation is an important initial step for bone formation during development as well as during remodelling and repair in the adult skeleton. This results in a heavily vascularized tissue where endothelial cells and skeletal cells are constantly in crosstalk to facilitate homeostasis, a process that is mediated by numerous environmental signals, including mechanical loading. Breakdown in this communication can lead to disease and/or poor fracture repair. Therefore, this study aimed to determine the role of mature bone cells in regulating angiogenesis, how this is influenced by a dynamic mechanical environment, and understand the mechanism by which this could occur. Herein, we demonstrate that both osteoblasts and osteocytes coordinate endothelial cell proliferation, migration, and blood vessel formation via a mechanically dependent paracrine mechanism. Moreover, we identified that this process is mediated via the secretion of extracellular vesicles (EVs), as isolated EVs from mechanically stimulated bone cells elicited the same response as seen with the full secretome, while the EV-depleted secretome did not elicit any effect. Despite mechanically activated bone cell-derived EVs (MA-EVs) driving a similar response to VEGF treatment, MA-EVs contain minimal quantities of this angiogenic factor. Lastly, a miRNA screen identified mechanoresponsive miRNAs packaged within MA-EVs which are linked with angiogenesis. Taken together, this study has highlighted an important mechanism in osteogenic-angiogenic coupling in bone and has identified the mechanically activated bone cell-derived EVs as a therapeutic to promote angiogenesis and potentially bone repair.

Funding

Science Foundation Ireland (SFI) Frontiers for the Future Grant SFI 19/FFP/6533

Irish Research Council Advanced Laureate Award EVIC [IRCLA/2019/49]

Horizon 2020 Research and Innovation Award EVPRO [814495]

History

Comments

The original article is available at https://journals.sagepub.com/

Published Citation

Shen N, et al. Mechanically activated mesenchymal-derived bone cells drive vessel formation via an extracellular vesicle mediated mechanism. J Tissue Eng. 2023;14:20417314231186918.

Publication Date

29 August 2023

PubMed ID

37654438

Department/Unit

  • School of Pharmacy and Biomolecular Sciences

Publisher

SAGE Publications Ltd,

Version

  • Published Version (Version of Record)