Fusion-Potential of Human Osteoclasts in vitro Reflects Age, Menopause, and in vivo Bone Resorption Levels of their Donors: A Possible Involvement of DC-STAMP

Anaïs Marie Julie Møller*, Jean-Marie Delaissé, Jacob Bastholm Olesen, Luisa M. do Canto, Silvia Regina Rogatto, Jonna Skov Madsen, Kent Søe*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

It is well established that multinucleation is central for osteoclastic bone resorption. However, our knowledge on the mechanisms regulating how many nuclei an osteoclast will have is limited. The objective of this study was to investigate donor-related variations in the fusion potential of in vitro-generated osteoclasts. Therefore, CD14+ monocytes were isolated from 49 healthy female donors. Donor demographics were compared to the in vivo bone biomarker levels and their monocytes’ ability to differentiate into osteoclasts, showing that: (1) C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) levels increase with age, (2) the number of nuclei per osteoclast in vitro increases with age, and 3) there is a positive correlation between the number of nuclei per osteoclast in vitro and CTX levels in vivo. Furthermore, the expression levels of the gene encoding dendritic cell-specific transmembrane protein (DCSTAMP ) of osteoclasts in vitro correlated positively with the number of nuclei per osteoclast, CTX levels in vivo, and donor age. Our results furthermore suggest that these changes in gene expression may be mediated through age-related changes in DNA methylation levels. We conclude that both intrinsic factors and age-induced increase in fusion potential of osteoclasts could be contributing factors for the enhanced bone resorption in vivo, possibly caused by increased expression levels of DCSTAMP.
Original languageEnglish
Article number6368
JournalInternational Journal of Molecular Sciences
Volume21
Issue number17
Number of pages16
ISSN1661-6596
DOIs
Publication statusPublished - 2. Sep 2020

Keywords

  • Aging
  • CTX
  • Cell fusion
  • DC-STAMP
  • DNA methylation
  • Epigenetics
  • Menopause
  • Multinucleation
  • Osteoclast
  • Osteoclastogenesis

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