A Bioreactor for 3D In Vitro Modeling of the Mechanical Stimulation of Osteocytes

Koh Meng Aw Yong, Eric Horst, Dylan Neale, Sonya Royzenblat, Joerg Lahann, Colin Greineder, Megan Weivoda, Geeta Mehta, Evan T. Keller

Research output: Contribution to journalArticlepeer-review

Abstract

The bone is a mechanosensitive organ that is also a common metastatic site for prostate cancer. However, the mechanism by which the tumor interacts with the bone microenvironment to further promote disease progression remains to be fully understood. This is largely due to a lack of physiological yet user-friendly models that limit our ability to perform in-depth mechanistic studies. Here, we report a tunable bioreactor which facilitates the 3D culture of the osteocyte cell line, MLO-Y4, in a hydroxyapatite/tricalcium phosphate (HA/TCP) scaffold under constant fluidic shear stress and tunable hydrostatic pressure within physiological parameters. Increasing hydrostatic pressure was sufficient to induce a change in the expression of several bone remodeling genes such as Dmp1, Rankl, and Runx2. Furthermore, increased hydrostatic pressure induced the osteocytes to promote the differentiation of the murine macrophage cell line RAW264.7 toward osteoclast-like cells. These results demonstrate that the bioreactor recapitulates the mechanotransduction response of osteocytes to pressure including the measurement of their functional ability in a 3D environment. In conclusion, the bioreactor would be useful for exploring the mechanisms of osteocytes in bone health and disease.

Original languageEnglish (US)
Article number797542
JournalFrontiers in Bioengineering and Biotechnology
Volume10
DOIs
StatePublished - Mar 25 2022

Keywords

  • bioreactor 3D cell culture
  • mechanotrasduction
  • osteoblast (OB)
  • osteocyte
  • prostate cancer

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Histology
  • Biomedical Engineering

Fingerprint

Dive into the research topics of 'A Bioreactor for 3D In Vitro Modeling of the Mechanical Stimulation of Osteocytes'. Together they form a unique fingerprint.

Cite this