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

McCully, Mark; Conde, João; Baptista, Pedro V.; Mullin, Margaret; Dalby, Matthew J.; Berry, Catherine C.

http://hdl.handle.net/10362/65496

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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.

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The author CCB wishes to acknowledge funding from the Biotechnology and Biological Sciences Research Council (BBSRC); BB/L008661/1. (https://www.bbsrc.ac.uk/); PVB was supported by the Unidade de Ciencias Biomoleculares Aplicadas-UCIBIO, which is financed by national funds from Fundacao para a Ciencia e a Tecnologia / Ministerio da Educacao e Ciencia (FCT/MEC) (https://www.fct.pt/) (UID/Multi/04378/2013) and co-financed by the European Regional Development Fund (ERDF) (http://ec.europa.eu/regional_policy/en/funding/erdf/) under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728); PP for PD/BD/105734/2014. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.