Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures

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...

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Autores principales: John W. Kennedy, P. Monica Tsimbouri, Paul Campsie, Shatakshi Sood, Peter G. Childs, Stuart Reid, Peter S. Young, Dominic R. M. Meek, Carl S. Goodyear, Matthew J. Dalby
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/810f83f7a49e40a688c667b930757c1d
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spelling oai:doaj.org-article:810f83f7a49e40a688c667b930757c1d2021-11-28T12:21:31ZNanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures10.1038/s41598-021-02139-92045-2322https://doaj.org/article/810f83f7a49e40a688c667b930757c1d2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02139-9https://doaj.org/toc/2045-2322Abstract 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.John W. KennedyP. Monica TsimbouriPaul CampsieShatakshi SoodPeter G. ChildsStuart ReidPeter S. YoungDominic R. M. MeekCarl S. GoodyearMatthew J. DalbyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
John W. Kennedy
P. Monica Tsimbouri
Paul Campsie
Shatakshi Sood
Peter G. Childs
Stuart Reid
Peter S. Young
Dominic R. M. Meek
Carl S. Goodyear
Matthew J. Dalby
Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures
description 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.
format article
author John W. Kennedy
P. Monica Tsimbouri
Paul Campsie
Shatakshi Sood
Peter G. Childs
Stuart Reid
Peter S. Young
Dominic R. M. Meek
Carl S. Goodyear
Matthew J. Dalby
author_facet John W. Kennedy
P. Monica Tsimbouri
Paul Campsie
Shatakshi Sood
Peter G. Childs
Stuart Reid
Peter S. Young
Dominic R. M. Meek
Carl S. Goodyear
Matthew J. Dalby
author_sort John W. Kennedy
title Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures
title_short Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures
title_full Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures
title_fullStr Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures
title_full_unstemmed Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures
title_sort nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/810f83f7a49e40a688c667b930757c1d
work_keys_str_mv AT johnwkennedy nanovibrationalstimulationinhibitsosteoclastogenesisandenhancesosteogenesisincocultures
AT pmonicatsimbouri nanovibrationalstimulationinhibitsosteoclastogenesisandenhancesosteogenesisincocultures
AT paulcampsie nanovibrationalstimulationinhibitsosteoclastogenesisandenhancesosteogenesisincocultures
AT shatakshisood nanovibrationalstimulationinhibitsosteoclastogenesisandenhancesosteogenesisincocultures
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AT dominicrmmeek nanovibrationalstimulationinhibitsosteoclastogenesisandenhancesosteogenesisincocultures
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