Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures

John W. Kennedy, Monica P. Tsimbouri, Paul Campsie, Shatakshi Sood, Peter G. Childs, Stuart Reid, Peter S. Young, Dominic R. M. Meek, Carl S. Goodyear, Matthew J. Dalby

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
30 Downloads (Pure)

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.
Original languageEnglish
Article number22741
Number of pages11
JournalScientific Reports
Volume11
DOIs
Publication statusPublished - 23 Nov 2021

Keywords

  • osteoporosis
  • bone density
  • metabolomics

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