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 language | English |
|---|---|
| Pages (from-to) | 77-86 |
| Number of pages | 10 |
| Journal | Cell Biochemistry and Function |
| Volume | 32 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2014 |
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Keywords
- Apoptosis
- Calcification
- Mesenchymal stem cell
- Necrosis
- Osteoblast
- Reactive oxygen species
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Clinical Biochemistry
Cite this
Necrotic and apoptotic cells serve as nuclei for calcification on osteoblastic differentiation of human mesenchymal stem cells in vitro. / Fujita, Hirofumi; Yamamoto, Masanao; Ogino, Tetsuya; Kobuchi, Hirotsugu; Ohmoto, Naoko; Aoyama, Eriko; Oka, Takashi; Nakanishi, Tohru; Inoue, Keiji; Sasaki, Junzo.
In: Cell Biochemistry and Function, Vol. 32, No. 1, 01.2014, p. 77-86.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Necrotic and apoptotic cells serve as nuclei for calcification on osteoblastic differentiation of human mesenchymal stem cells in vitro
AU - Fujita, Hirofumi
AU - Yamamoto, Masanao
AU - Ogino, Tetsuya
AU - Kobuchi, Hirotsugu
AU - Ohmoto, Naoko
AU - Aoyama, Eriko
AU - Oka, Takashi
AU - Nakanishi, Tohru
AU - Inoue, Keiji
AU - Sasaki, Junzo
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Calcification
KW - Mesenchymal stem cell
KW - Necrosis
KW - Osteoblast
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=84891835898&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84891835898&partnerID=8YFLogxK
U2 - 10.1002/cbf.2974
DO - 10.1002/cbf.2974
M3 - Article
C2 - 23657822
AN - SCOPUS:84891835898
VL - 32
SP - 77
EP - 86
JO - Cell Biochemistry and Function
JF - Cell Biochemistry and Function
SN - 0263-6484
IS - 1
ER -