| RRC ID |
63974
|
| 著者 |
Suzuki R, Fujiwara Y, Saito M, Arakawa S, Shirakawa JI, Yamanaka M, Komohara Y, Marumo K, Nagai R.
|
| タイトル |
Intracellular Accumulation of Advanced Glycation End Products Induces Osteoblast Apoptosis Via Endoplasmic Reticulum Stress.
|
| ジャーナル |
J Bone Miner Res
|
| Abstract |
Osteoporosis is an aging-associated disease that is attributed to excessive osteoblast apoptosis. It is known that the accumulation of advanced glycation end products (AGEs) in bone extracellular matrix deteriorates osteoblast functions. However, little is known about the interaction between intracellular AGE accumulation and the induction of osteoblast apoptosis. In this study, we investigated the effect of intracellular AGE accumulation on osteoblast apoptosis in vitro and in vivo. In vitro, murine osteoblastic MC3T3-E1 cells were treated with glycolaldehyde (GA), an AGE precursor. GA-induced intracellular AGE accumulation progressed in time- and dose-dependent manners, followed by apoptosis induction. Intracellular AGE formation also activated endoplasmic reticulum (ER) stress-related proteins (such as glucose-regulated protein 78, inositol-requiring protein-1α (IRE1α), and c-Jun N-terminal kinase) and induced apoptosis. In agreement, treatment with the ER stress inhibitor 4-phenylbutyric acid and knocking down IRE1α expression ameliorated osteoblast apoptosis. Furthermore, the ratio between AGE- and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive osteoblasts in human vertebral bodies was significantly higher in an elderly group than in a younger group. A positive linear correlation between the ratio of AGE-positive and TUNEL-positive osteoblasts (r = 0.72) was also observed. Collectively, these results indicate that AGEs accumulated in osteoblasts with age and that intracellular AGE accumulation induces apoptosis via ER stress. These findings offer new insight into the mechanisms of osteoblast apoptosis and age-related osteoporosis. © 2020 American Society for Bone and Mineral Research.
|
| 巻・号 |
35(10)
|
| ページ |
1992-2003
|
| 公開日 |
2020-10-1
|
| DOI |
10.1002/jbmr.4053
|
| PMID |
32427355
|
| MeSH |
3T3 Cells
Animals
Apoptosis*
Endoplasmic Reticulum Stress*
Endoribonucleases
Glycation End Products, Advanced / metabolism*
Humans
Mice
Osteoblasts / cytology*
Protein Serine-Threonine Kinases
|
| IF |
5.854
|
| リソース情報 |
| ヒト・動物細胞 |
MC3T3-E1(RCB1126) |
