Real-time quantification of osteoclastic resorptive activity by electric cell-substrate impedance sensing

Ineke D.C. Jansen, Thijs van Velzen, Teun J. de Vries, Robert Szulcek, Jack J.W.A. van Loon*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

In several diseases, bone resorption by osteoclasts is dysregulated. Thus far, no simple technique for real-time measurement of resorption is available. Here, we introduce an impedimetric bioassay for real-time monitoring of resorption by making use of the electrical insulating properties of the resorbable substrate calcium phosphate. Different chemical stimuli were applied to (pre)osteoclasts cultured on a layer of calcium phosphate in multi-well plates containing electrodes. By this, osteoclast activity can be measured continuously over days, and the effects of stimulating or inhibiting factors can be quantified. When cells were cultured in the presence of an inflammatory factor such as IL-1β, the resorptive activity started earlier. The measured decline in resistance was higher at culture day 5 than at cultures with M-CSF or M-CSF + RANKL (M-CSF norm. Resistance = 1, M-CSF + RANKL = 0.7, M-CSF + RANKL + IL-1β = 0.5). However, at day 11, this difference had nearly disappeared. Likewise, bisphosphonates were shown to inhibit osteoclastic activity. Our findings illustrate the importance of real-time monitoring; wherefore, this method has high potential not only for the study of osteoclast resorptive activity in the context of osteoclast function and diseases but also could find application in high-throughput drug-testing studies.

Original languageEnglish
Article number921066
Pages (from-to)1-9
Number of pages9
JournalFrontiers in Cell and Developmental Biology
Volume10
DOIs
Publication statusPublished - 19 Aug 2022

Bibliographical note

Funding Information:
This work was partially supported by the Dutch CardioVascular Alliance (DCVA) (2012-08, 2014-11) awarded to the Phaedra and the RECONNECT consortium as well as the Impulse Grant 2018 awarded to the Phaedra IMPACT consortium. These Grants include collective funding from the Dutch Heart Foundation, the Dutch Federation of University Medical Centers, Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences.

Publisher Copyright:
Copyright © 2022 Jansen, van Velzen, de Vries, Szulcek and van Loon.

Keywords

  • bone
  • ECIS
  • osteoclast
  • real-time quantification
  • resorption
  • sensor

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