Alpinumisoflavone rescues glucocorticoid-induced apoptosis of osteocytes via suppressing Nox2-dependent ROS generation
Authors: Leixiang Han
Wei Cong
Jun Yin
Journal: Pharmacological Reports (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: AMPK; Alpinumisoflavone; Apoptosis; Nox2; Osteocyte
Affiliations: Qilu Hospital of Shandong University, Qingdao, Shandong, China., Qilu Hospital of Shandong University, Qingdao, Shandong, China. Electronic address: .

Abstract:  Background: Long term use of glucocorticoids is one of the most common causes of secondary osteoporosis. Osteocyte, the most abundant cell type in bone, coordinates the function of osteoblast and osteoclast. This study evaluates the protective effect of alpinumisoflavone (AIF), a naturally occurring flavonoid compound, on dexamethasone (Dex)-induced apoptosis of osteocytes. Methods: MLO-Y4 cell was used as a cell model. The effect of AIF on the cell viability was assessed by MTT assay. Apoptosis of MYL-Y4 cells was determined by DNA fragment detection ELISA kit and flow cytometry. Intracellular ROS level was determined by DCFH-DA staining. mRNA and protein expression of target genes were determined by qRT-PCR and western blot, respectively. Results: AIF effectively protected MLO-Y4 cells against Dex-induced apoptosis, which was associated with attenuation of Dex-induced ROS generation in MLO-Y4 cells. Furthermore, our data indicated that the expression of NAD(P)H oxidase 2 (Nox2) was suppressed by AIF, which in turn mediated the attenuating effect on Dex-induced ROS generation and apoptosis in MLO-Y4 cells. Moreover, our results showed that AIF modulated the expression of Nox2 by activating AMPK signaling. Conclusion: AIF activated AMPK-dependent Nox2 signaling pathway to suppress Dex-induced ROS production in cultured osteocytes, which might explain its anti-apoptotic effect. These results indicate that activation of AMPK pathway by AIF could have beneficial effects on bone damage induced by excessive oxidative stress and osteocyte apoptosis. 

Retracted: Yes

PubPeer comments:
 Fig 1C, Effect of AIF on Dex-induced apoptosis in MLO-Y4 cells. ... (C)AIF protects Dex-induced apoptosis in MLO-Y4 cells, as determined by flow cytometry ; and 3D,  AIF attenuates Dex-induced ROS generation by suppressing Nox2 expression.... (D) Nox2 overexpression significantly abrogated the protective effect of AIF on Dex-induced apoptosis in MLO-Y4 cells, as determined by flow cytometry. ![file] Other versions of these panels can be found across a sprawling oeuvre of papers, as in this montage: ![] , 
 2021 retraction. https: link.springer.com article 10.1007 s43440-020-00211-1 The Editor in Chief has retracted this article [1] because of concerns regarding similarities between Fig. 1C and Fig. 3D, which question the integrity of the data. The authors did not respond to request for an explanation or additional data. The Editor-in-Chief therefore no longer has confidence in the integrity of the data in this article. None of the authors has responded to any correspondence from the editor or publisher about this retraction. Reference 1. Yin J, Han L, Cong W. Alpinumisoflavone rescues glucocorticoid-induced apoptosis of osteocytes via suppressing Nox2-dependent ROS generation. Pharmacol Rep. 2018;70:270u20136. https: doi.org 10.1016 j.pharep.2017.11.001 ,