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language
eng
Author
Yamaguchi, Toru
Okazaki, Kyoko
Tanaka, Ken-ichiro
Description
In diabetic patients, advanced glycation end products (AGEs) cause bone fragility because of deterioration of bone quality. We previously showed that AGEs suppressed the mineralization of mouse stromal ST2 cells. TGF-β is abundant in bone, and enhancement of its signal causes bone quality deterioration. However, whether TGF-β signaling is involved in the AGE-induced suppression of mineralization during the osteoblast lineage remains unknown. We therefore examined the roles of TGF-β in the AGE-induced suppression of mineralization of ST2 cells and human mesenchymal stem cells. AGE3 significantly (P < .001) inhibited mineralization in both cell types, whereas transfection with small interfering RNA for the receptor for AGEs (RAGEs) significantly (P < .05) recovered this process in ST2 cells. AGE3 increased (P < .001) the expression of TGF-β mRNA and protein, which was partially antagonized by transfection with RAGE small interfering RNA. Treatment with a TGF-β type I receptor kinase inhibitor, SD208, recovered AGE3-induced decreases in osterix (P < .001) and osteocalcin (P < .05) and antagonized the AGE3-induced increase in Runx2 mRNA expression in ST2 cells (P < .001). Moreover, SD208 completely and dose dependently rescued AGE3-induced suppression of mineralization in both cell types. In contrast, SD208 intensified AGE3-induced suppression of cell proliferation as well as AGE3-induced apoptosis in proliferating ST2 cells. These findings indicate that, after cells become confluent, AGE3 partially inhibits the differentiation and mineralization of osteoblastic cells by binding to RAGE and increasing TGF-β expression and secretion. They also suggest that TGF-β adversely affects bone quality not only in primary osteoporosis but also in diabetes-related bone disorder.
Subject
Advanced Glycation end Products (AGEs)
Bone quality deterioration
Osteoblast differentiation
TGF-β
Journal Title
Endocrinology
Volume
115
Issue
7
Start Page
2402
End Page
2410
ISSN
00137227
Published Date
2014-07-01
DOI
DOI Date
2017-04-10
PubMed ID
NCID
AA12024486
Publisher
Endocrine Society
NII Type
Journal Article
Format
PDF
Rights
© 2014 by the Endocrine Society
Text Version
著者版
Gyoseki ID
e26810
e27003
e26885
OAI-PMH Set
Faculty of Medicine
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