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Title: Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells

Abstract

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-kB 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{sup −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 deteriorationmore » by inducing osteocyte apoptosis. PTH may effectively treat these pathological processes and improve osteocyte function. - Highlights: • AGEs are involved in bone quality deterioration in diabetes mellitus (DM). • AGEs increased sclerostin as well as apoptosis, and decreased RANKL in osteocytes. • The effects of AGEs on osteocyte function were antagonized by human PTH-(1–34). • AGEs may cause low bone turnover and cortical porosity in DM. • PTH may be effective in bone quality deterioration by improving osteocyte function.« less

Authors:
; ; ;
Publication Date:
OSTI Identifier:
22462056
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 461; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BONE CELLS; DIABETES MELLITUS; GLUCOSE; HORMONES; LIGANDS; MESSENGER-RNA; POROSITY; RECEPTORS; SKELETON

Citation Formats

Tanaka, Ken-ichiro, E-mail: ken1nai@med.shimane-u.ac.jp, Yamaguchi, Toru, E-mail: yamaguch@med.shimane-u.ac.jp, Kanazawa, Ippei, E-mail: ippei.k@med.shimane-u.ac.jp, and Sugimoto, Toshitsugu, E-mail: sugimoto@med.shimane-u.ac.jp. Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.02.091.
Tanaka, Ken-ichiro, E-mail: ken1nai@med.shimane-u.ac.jp, Yamaguchi, Toru, E-mail: yamaguch@med.shimane-u.ac.jp, Kanazawa, Ippei, E-mail: ippei.k@med.shimane-u.ac.jp, & Sugimoto, Toshitsugu, E-mail: sugimoto@med.shimane-u.ac.jp. Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells. United States. doi:10.1016/J.BBRC.2015.02.091.
Tanaka, Ken-ichiro, E-mail: ken1nai@med.shimane-u.ac.jp, Yamaguchi, Toru, E-mail: yamaguch@med.shimane-u.ac.jp, Kanazawa, Ippei, E-mail: ippei.k@med.shimane-u.ac.jp, and Sugimoto, Toshitsugu, E-mail: sugimoto@med.shimane-u.ac.jp. Fri . "Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells". United States. doi:10.1016/J.BBRC.2015.02.091.
@article{osti_22462056,
title = {Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells},
author = {Tanaka, Ken-ichiro, E-mail: ken1nai@med.shimane-u.ac.jp and Yamaguchi, Toru, E-mail: yamaguch@med.shimane-u.ac.jp and Kanazawa, Ippei, E-mail: ippei.k@med.shimane-u.ac.jp and Sugimoto, Toshitsugu, E-mail: sugimoto@med.shimane-u.ac.jp},
abstractNote = {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-kB 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{sup −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. - Highlights: • AGEs are involved in bone quality deterioration in diabetes mellitus (DM). • AGEs increased sclerostin as well as apoptosis, and decreased RANKL in osteocytes. • The effects of AGEs on osteocyte function were antagonized by human PTH-(1–34). • AGEs may cause low bone turnover and cortical porosity in DM. • PTH may be effective in bone quality deterioration by improving osteocyte function.},
doi = {10.1016/J.BBRC.2015.02.091},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 461,
place = {United States},
year = {2015},
month = {5}
}