Wnt/β-catenin signaling plays an important role in the protective effects of FDP-Sr against oxidative stress induced apoptosis in MC3T3-E1 cell

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• 作者：Huan-Huan Qi^a ; ^&dagger ; ; Jun Bao^b ; ^&dagger ; ; Qi Zhang^a ; ^{nancyzhang03@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Bo Ma^a ; ^{mabo19821221@163.com" class="auth_mail" title="E-mail the corresponding author} ; Gui-Ying Gu^a ; Peng-Ling Zhang^b ; Gang Ou-Yang^b ; Zi-Mei Wu^c ; Han-Jie Ying^d ; Ping-Kai Ou-Yang^d
• 关键词：FDP-Sr ; Osteoporosis ; Oxidative stress ; Apoptosis ; Wnt/β-catenin signaling
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 October 2016
• 年：2016
• 卷：26
• 期：19
• 页码：4720-4723
• 全文大小：1321 K

文摘

Strontium fructose 1,6-diphosphate (FDP-Sr) is a new strontium-containing compound. The primary aim of this study was to clarify whether the structure component of FDP-Sr, FDP could benefit the protective effect of Sr (II) against oxidative stress induced apoptosis, and meanwhile to further explore the important role of Wnt/β-catenin signaling in the anti-apoptosis effect of FDP-Sr in response to oxidative stress induced by H₂O₂ in an osteoblastic MC3T3-E1 cell line. Results showed that FDP-Sr could improve the osteoblastic differentiation under oxidative stress with induced cell proliferation and improved mineralization. The inhibition effect of FDP-Sr on cell apoptosis induced by H₂O₂ was proved by reduced reactive oxygen species production and activated caspase3. Under oxidative stress, mRNA and protein levels of phospho-β-catenin reduced, while β-catenin increased in the FDP-Sr treatment cell, leaded to the up-regulations of Runx2 and OPG at both mRNA and protein levels, finally improved the differentiation of osteoblasts. By the engagement of Wnt/β-catenin pathway’s inhibitor (XAV-939), the protective effects of FDP-Sr on osteoblastic differentiation against oxidative stress were repressed along with inhibited wnt/β-catenin signaling and reduced mRNA and protein levels of Runx2 and OPG. In conclusion, FDP-Sr was demonstrated to protect osteoblast differentiation from oxidative damage induced by H₂O₂ through up-regulation of Wnt/β-catenin signaling, and FDP in FDP-Sr was able to directly improve the oxidative stress injury through its ROS scavenging ability.