PMID- 23933252
OWN - NLM
STAT- MEDLINE
DCOM- 20131104
LR  - 20171116
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 438
IP  - 3
DP  - 2013 Aug 30
TI  - Advanced glycation end products suppress osteoblastic differentiation of stromal 
      cells by activating endoplasmic reticulum stress.
PG  - 463-7
LID - S0006-291X(13)01311-9 [pii]
LID - 10.1016/j.bbrc.2013.07.126 [doi]
AB  - Advanced glycation end products (AGEs) are involved in bone quality deterioration 
      in diabetes mellitus. We previously showed that AGE2 or AGE3 inhibited 
      osteoblastic differentiation and mineralization of mouse stromal ST2 cells, and 
      also induced apoptosis and decreased cell growth. Although quality management for 
      synthesized proteins in endoplasmic reticulum (ER) is crucial for the maturation 
      of osteoblasts, the effects of AGEs on ER stress in osteoblast lineage are 
      unknown. We thus examined roles of ER stress in AGE2- or AGE3-induced suppression 
      of osteoblastogenesis of ST2 cells. An ER stress inducer, thapsigargin (TG), 
      induced osteoblastic differentiation of ST2 cells by increasing the levels of 
      Osterix, type 1 collagen (Col1), alkaline phosphatase (ALP) and osteocalcin (OCN) 
      mRNA. AGE2 or AGE3 suppressed the levels of ER stress sensors such as IRE1alpha, ATF6 
      and OASIS, while they increased the levels of PERK and its downstream molecules, 
      ATF4. A reduction in PERK level by siRNA did not affect the AGEs-induced 
      suppression of the levels of Osterix, Col1 and OCN mRNA. In conclusion, AGEs 
      inhibited the osteoblastic differentiation of stromal cells by suppressing ER 
      stress sensors and accumulating abnormal proteins in the cells. This process 
      might accelerate AGEs-induced suppression of bone formation found in diabetes 
      mellitus.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Tanaka, Ken-ichiro
AU  - Tanaka K
AD  - Department of Internal Medicine 1, Shimane University Faculty of Medicine, Izumo, 
      Japan. ken1nai@med.shimane-u.ac.jp
FAU - Yamaguchi, Toru
AU  - Yamaguchi T
FAU - Kaji, Hiroshi
AU  - Kaji H
FAU - Kanazawa, Ippei
AU  - Kanazawa I
FAU - Sugimoto, Toshitsugu
AU  - Sugimoto T
LA  - eng
PT  - Journal Article
DEP - 20130807
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Glycation End Products, Advanced)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cell Differentiation/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Endoplasmic Reticulum Stress
MH  - Glycation End Products, Advanced/*pharmacology
MH  - Mice
MH  - Osteoblasts/*cytology
MH  - Stromal Cells/*cytology/drug effects
MH  - Thapsigargin/pharmacology
OTO - NOTNLM
OT  - ATF
OT  - Advanced glycation end products
OT  - Bone
OT  - Diabetes
OT  - Endoplasmic reticulum stress
OT  - IRE
OT  - OASIS
OT  - Osteoblastogenesis
OT  - PERK
OT  - Stromal cells
OT  - activating transcription factor
OT  - inositol-requiring transmembrane kinase and endonuclease
OT  - old astrocyte specifically induced substance
OT  - protein kinase RNA-like endoplasmic reticulum kinase
EDAT- 2013/08/13 06:00
MHDA- 2013/11/05 06:00
CRDT- 2013/08/13 06:00
PHST- 2013/07/26 00:00 [received]
PHST- 2013/07/31 00:00 [accepted]
PHST- 2013/08/13 06:00 [entrez]
PHST- 2013/08/13 06:00 [pubmed]
PHST- 2013/11/05 06:00 [medline]
AID - S0006-291X(13)01311-9 [pii]
AID - 10.1016/j.bbrc.2013.07.126 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2013 Aug 30;438(3):463-7. doi: 
      10.1016/j.bbrc.2013.07.126. Epub 2013 Aug 7.