Advanced Glycation End Product 3 (AGE3) Increases Apoptosis and the Expression of Sclerostin by Stimulating TGF-β Expression and Secretion in Osteocyte-Like MLO-Y4-A2 Cells

Masakazu Notsu, Ippei Kanazawa, Ayumu Takeno, Maki Yokomoto-Umakoshi, Ken ichiro Tanaka, Toru Yamaguchi, Toshitsugu Sugimoto

研究成果: Contribution to journalArticle査読

18 被引用数 (Scopus)

抄録

Advanced glycation end products (AGEs) cause bone fragility due to deterioration in bone quality. We previously reported that AGE3 induced apoptosis and inhibited differentiation via increased transforming growth factor (TGF)-β signaling in osteoblastic cells. Additionally, we demonstrated that AGE3 increased apoptosis and sclerostin expression and decreased receptor activator of nuclear factor-κB ligand (RANKL) expression in osteocyte-like cells. However, it remains unclear whether TGF-β signaling is involved in the effects of AGEs on apoptosis and the expression of sclerostin and RANKL in osteocytes. Effects of AGE3 on apoptosis of mouse osteocyte-like MLO-Y4-A2 cells were examined by DNA fragmentation ELISA. Expression of TGF-β, sclerostin, and RANKL was evaluated using real-time PCR, Western blotting, and ELISA kits. To block TGF-β signaling, we used SD208, a TGF-β type I receptor kinase inhibitor. AGE3 (200 µg/mL) significantly increased apoptosis and mRNA expression of Sost, the gene encoding sclerostin, and decreased Rankl mRNA expression in MLO-Y4-A2 cells. AGE3 significantly increased the expression of TGF-β. Co-incubation of SD208 with AGE3 significantly rescued AGE3-induced apoptosis in a dose-dependent manner. Moreover, SD208 restored AGE3-increased mRNA and protein expression of sclerostin. In contrast, SD208 did not affect AGE3-decreased mRNA and protein expression of RANKL. These findings suggest that AGE3 increases apoptosis and sclerostin expression through increasing TGF-β expression in osteocytes, and that AGE3 decreases RANKL expression independent of TGF-β signaling.

本文言語英語
ページ(範囲)402-411
ページ数10
ジャーナルCalcified Tissue International
100
4
DOI
出版ステータス出版済み - 4 1 2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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