Nanoscale vibration to modulate osteoclastogenesis

Kennedy, John William (2020) Nanoscale vibration to modulate osteoclastogenesis. MD thesis, University of Glasgow.

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Abstract

Mechanical factors have been shown to significantly influence stem cell differentiation and fate. Researchers have demonstrated that nanoscale vibration can promote osteogenesis in isolated mesenchymal stem cell (MSC) cultures. In the bone marrow niche, there is a co-dependent existence between MSCs and cells from the haematopoietic lineage (HSCs), particularly osteoclasts. While MSC derived osteoblasts stimulate new bone formation, osteoclasts resorb bone. Given the close overlap between these two cells types, an investigation in to the effect of nanoscale vibration on osteoclasts was required.

Two culture methods were used: an isolated culture of osteoclasts and osteoclast-precursors, and a co-culture of bone marrow stromal cells and bone marrow haematopoietic cells. Vibration was produced with the Nanokick bioreactor – a recently developed technology that facilitates the delivery of accurate and reproducible nanoscale vertical displacements. This bioreactor allows otherwise standard cell culture techniques to be used. A range of experiments was used to investigate the effect of nanoscale vibration, including immunostaining, resorption analysis, RT-qPCR, ELISA and metabolomics.

Nanoscale vibration was found to influence osteoclast differentiation and function. A reduction in osteoclast numbers was observed in both culture conditions. Furthermore, less resorption occurred in the nanokick group. There was no significant impairment in osteoblast development or function when osteoclasts were present, with evidence of increased cytoskeleton tension and mineralisation following stimulation. A number of changes in gene, protein and regulations were observed, suggesting a state of lower inflammation in the nanokick group.

It is hoped that these results will provide further evidence to validate the use of the Nanokick bioreactor as a method of producing tissue-engineered bone graft for clinical applications.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Nanoscale, vibration, osteoclast, bone, tissue engineering, regenerative medicine, bioreactor, orthopaedics.
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history > QH301 Biology
R Medicine > R Medicine (General)
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Supervisor's Name: Dalby, Professor Matthew J.
Date of Award: 2020
Depositing User: Mr John William Kennedy
Unique ID: glathesis:2020-81278
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 09 Apr 2020 08:35
Last Modified: 03 May 2020 12:51
URI: http://theses.gla.ac.uk/id/eprint/81278

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