Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures

Kennedy, J. W., Tsimbouri, M. , Campsie, P., Sood, S., Childs, P. G., Reid, S., Young, P. S., Meek, D. R. M., Goodyear, C. S. and Dalby, M. J. (2021) Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures. Scientific Reports, 11, 22741. (doi: 10.1038/s41598-021-02139-9)

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Abstract

Models of bone remodelling could be useful in drug discovery, particularly if the model is one that replicates bone regeneration with reduction in osteoclast activity. Here we use nanovibrational stimulation to achieve this in a 3D co-culture of primary human osteoprogenitor and osteoclast progenitor cells. We show that 1000 Hz frequency, 40 nm amplitude vibration reduces osteoclast formation and activity in human mononuclear CD14+ blood cells. Additionally, this nanoscale vibration both enhances osteogenesis and reduces osteoclastogenesis in a co-culture of primary human bone marrow stromal cells and bone marrow hematopoietic cells. Further, we use metabolomics to identify Akt (protein kinase C) as a potential mediator. Akt is known to be involved in bone differentiation via transforming growth factor beta 1 (TGFβ1) and bone morphogenetic protein 2 (BMP2) and it has been implicated in reduced osteoclast activity via Guanine nucleotide-binding protein subunit α13 (Gα13). With further validation, our nanovibrational bioreactor could be used to help provide humanised 3D models for drug screening.

Item Type:Articles
Additional Information:Funding: This work was funded by The Engineering and Physical Sciences Research Council (grant number EP/N013905/1) & The Royal College of Surgeons Edinburgh (grant number SPPG/17/113).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Young, Dr Peter and Sood, Dr Shatakshi and Dalby, Professor Matthew and Tsimbouri, Dr Monica and Goodyear, Professor Carl
Authors: Kennedy, J. W., Tsimbouri, M., Campsie, P., Sood, S., Childs, P. G., Reid, S., Young, P. S., Meek, D. R. M., Goodyear, C. S., and Dalby, M. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN:2045-2322
ISSN (Online):2045-2322
Published Online:23 November 2021
Copyright Holders:Copyright © The Author(s) 2021
First Published:First published in Scientific Reports 11: 22741
Publisher Policy:Reproduced under a Creative Commons licence
Data DOI:10.5525/gla.researchdata.1090

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172525Developing the NanoKick bioreactor to enable tissue engineered bone graft and use of metabolomics to identify bone specific drug candidatesMatthew DalbyEngineering and Physical Sciences Research Council (EPSRC)EP/N013905/1Institute of Molecular, Cell & Systems Biology