Necrotic and apoptotic cells serve as nuclei for calcification on osteoblastic differentiation of human mesenchymal stem cells in vitro

Hirofumi Fujita, Masanao Yamamoto, Tetsuya Ogino, Hirotsugu Kobuchi, Naoko Ohmoto, Eriko Aoyama, Takashi Oka, Tohru Nakanishi, Keiji Inoue, Junzo Sasaki

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A close relationship between cell death and pathological calcification has recently been reported, such as vascular calcification in atherosclerosis. However, the roles of cell death in calcification by osteoblast lineage have not been elucidated in detail. In this study, we investigated whether cell death is involved in the calcification on osteoblastic differentiation of human bone marrow mesenchymal stem cells (hMSC) under osteogenic culture in vitro. Apoptosis and necrosis occurred in an osteogenic culture of hMSC, and cell death preceded calcification. The generation of intracellular reactive oxygen species, chromatin condensation and fragmentation, and caspase-3 activation increased in this culture. A pan-caspase inhibitor (Z-VAD-FMK) and anti-oxidants (Tiron and n-acetylcysteine) inhibited osteogenic culture-induced cell death and calcification. Furthermore, calcification was significantly promoted by the addition of necrotic dead cells or its membrane fraction. Spontaneously dead cells by osteogenic culture and exogenously added necrotic cells were surrounded by calcium deposits. Induction of localized cell death by photodynamic treatment in the osteogenic culture resulted in co-localized calcification. These findings show that necrotic and apoptotic cell deaths were induced in an osteogenic culture of hMSC and indicated that both necrotic and apoptotic cells of osteoblast lineage served as nuclei for calcification on osteoblastic differentiation of hMSC in vitro.

Original languageEnglish
Pages (from-to)77-86
Number of pages10
JournalCell biochemistry and function
Volume32
Issue number1
DOIs
Publication statusPublished - Jan 2014

Keywords

  • Apoptosis
  • Calcification
  • Mesenchymal stem cell
  • Necrosis
  • Osteoblast
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

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