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language
eng
Author
Tanaka, Ken-ichiro
Yamaguchi, Toru
Description
In diabetes mellitus (DM), high glucose (HG) and advanced glycation end products (AGEs) are involved in bone quality deterioration. Osteocytes produce sclerostin and receptor activator of nuclear factor-кB ligand (RANKL) and regulate osteoblast and osteoclast function. However, whether HG or AGEs directly affect osteocytes and regulate sclerostin and RANKL production is unknown. Here, we examined the effects of HG, AGE2, and AGE3 on the expression of sclerostin and RANKL and on apoptosis in osteocyte-like MLO-Y4-A2 cells. Treatment of the cells with 22 mM glucose, 100 μg/mL either AGE2 or AGE3 significantly increased the expression of sclerostin protein and mRNA; however, both AGEs, but not glucose, significantly decreased the expression of RANKL protein and mRNA. Moreover, treatment of the cells with HG, AGE2, or AGE3 for 72 h induced significant apoptosis. These detrimental effects of HG, AGE2, and AGE3 on sclerostin and RANKL expressions and on apoptosis were antagonized by pretreatment of the cells with 10^<-8> M human parathyroid hormone (PTH)-(1-34). Thus, HG and AGEs likely suppress bone formation by increasing sclerostin expression in osteocytes, whereas AGEs suppress bone resorption by decreasing RANKL expression. Together, these processes may cause low bone turnover in DM. In addition, HG and AGEs may cause cortical bone deterioration by inducing osteocyte apoptosis. PTH may effectively treat these pathological processes and improve osteocyte function.
Subject
Advanced glycation end products
Osteocyte
Sclerostin
Receptor activator of nuclear factor-кB ligand
Parathyroid hormone
Journal Title
Biochemical and biophysical research communications
Volume
461
Issue
2
Start Page
193
End Page
199
ISSN
0006291X
Published Date
2015-05
DOI
DOI Date
2017-04-10
PubMed ID
Publisher
Elsevier
NII Type
Journal Article
Format
PDF
Rights
© 2015 Elsevier Inc. All rights reserved.
Text Version
著者版
Gyoseki ID
e26998
e28548
e28615
OAI-PMH Set
Faculty of Medicine
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