Nanoparticle-antagomiR based targeting of miR-31 to induce osterix and osteocalcin expression in mesenchymal stem cells

Mccully, M., Conde, J., Baptista, P. V., Mullin, M., Dalby, M. J. and Berry, C. C. (2018) Nanoparticle-antagomiR based targeting of miR-31 to induce osterix and osteocalcin expression in mesenchymal stem cells. PLoS ONE, 13(2), e0192562. (doi:10.1371/journal.pone.0192562) (PMID:29444183) (PMCID:PMC5812622)

Mccully, M., Conde, J., Baptista, P. V., Mullin, M., Dalby, M. J. and Berry, C. C. (2018) Nanoparticle-antagomiR based targeting of miR-31 to induce osterix and osteocalcin expression in mesenchymal stem cells. PLoS ONE, 13(2), e0192562. (doi:10.1371/journal.pone.0192562) (PMID:29444183) (PMCID:PMC5812622)

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Abstract

Mesenchymal stem cells are multipotent adult stem cells capable of generating bone, cartilage and fat, and are thus currently being exploited for regenerative medicine. When considering osteogenesis, developments have been made with regards to chemical induction (e.g. differentiation media) and physical induction (e.g. material stiffness, nanotopography), targeting established early transcription factors or regulators such as runx2 or bone morphogenic proteins and promoting increased numbers of cells committing to osteo-specific differentiation. Recent research highlighted the involvement of microRNAs in lineage commitment and terminal differentiation. Herein, gold nanoparticles that confer stability to short single stranded RNAs were used to deliver MiR-31 antagomiRs to both pre-osteoblastic cells and primary human MSCs in vitro. Results showed that blocking miR-31 led to an increase in osterix protein in both cell types at day 7, with an increase in osteocalcin at day 21, suggesting MSC osteogenesis. In addition, it was noted that antagomiR sequence direction was important, with the 5 prime reading direction proving more effective than the 3 prime. This study highlights the potential that miRNA antagomiR-tagged nanoparticles offer as novel therapeutics in regenerative medicine.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mccully, Mr Mark and Berry, Dr Catherine and Mullin, Mrs Margaret and Dalby, Professor Matthew
Authors: Mccully, M., Conde, J., Baptista, P. V., Mullin, M., Dalby, M. J., and Berry, C. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Published Online:14 February 2018
Copyright Holders:Copyright © 2018 McCully et al.
First Published:First published in PLoS ONE 13(2):e0192562
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
619691Nanoparticles and nanotopography: a nano-toolbox to control stem cell self-renewal via microRNAsCatherine BerryBiotechnology and Biological Sciences Research Council (BBSRC)BB/L008661/1RI MOLECULAR CELL & SYSTEMS BIOLOGY