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A novel BMP2 secretagogue ameliorates glucocorticoid induced oxidative stress in osteoblasts by activating NRF2 dependent survival while promoting Wnt/ β-catenin mediated osteogenesis
Free Radic Biol Med. 2022 Aug 10:S0891-5849(22)00514-7. doi: 10.1016/j.freeradbiomed.2022.08.007. Online ahead of print.ABSTRACTIn our previous study, a novel BMP2 secretagogue was synthesized belonging to a class of galloyl conjugates of flavanones, with remarkable osteogenic potential that promoted bone regeneration. We aimed to establish the protective effect of our compound against bone loss that co-exists with excess Glucocorticoid (GC) therapy. GC therapy induces osteoblast damage leading to apoptosis by increasing reactive oxygen species (ROS). Our results delineate that compound 5e (a BMP2 secretagogue) activates N...
Source: Free Radical Biology and Medicine - August 13, 2022 Category: Biology Authors: Divya Rai Ashish Kumar Tripathi Anirban Sardar Alka Raj Pandey Shradha Sinha Kunal Chutani Geeta Dhaniya Priyanka Kothari Koneni V Sashidhara Ritu Trivedi Source Type: research

Chlorogenic acid promotes the Nrf2/HO-1 anti-oxidative pathway by activating p21Waf1/Cip1 to resist dexamethasone-induced apoptosis in osteoblastic cells.
Abstract In a previous study, p21Waf1/Cip1 (p21) promoted activation of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, which has an important role in regulating apoptosis triggered by oxidative stress and inhibiting development of osteoporosis. Chlorogenic acid (CGA) has a strong protective effect on osteoporosis, closely related to activating the Nrf2/HO-1 pathway. However, whether CGA can resist apoptosis by regulating p21 and consequently promote activation of the Nrf2/HO-1 pathway needs further investigation. MC3T3-E1 cells were treated with dexamethasone (Dex), with or without ...
Source: Free Radical Biology and Medicine - April 16, 2019 Category: Biology Authors: Han D, Gu X, Gao J, Wang Z, Liu G, Barkema HW, Han B Tags: Free Radic Biol Med Source Type: research

Z-Guggulsterone attenuates glucocorticoid-induced osteoporosis through activation of Nrf2/HO-1 signaling
Publication date: Available online 21 March 2019Source: Life SciencesAuthor(s): Yier Xu, Jian Guan, Jianyu Xu, Shuilin Chen, Guicai SunAbstractAimsThe present study aims to investigate the protective effect and underlying mechanism of Z-Guggulsterone (Z-GS), an active component from myrrh, on glucocorticoid-induced osteoporosis (GIO).Main methodsGIO rats were used to simulate osteoporosis in vivo while MC3T3-E1 cells were induced to osteoblast differentiation and treated with dexamethasone to simulate osteoporosis in vitro. The rats and cells were treated with Z-GS according to the protocol. The bone mineral density, biome...
Source: Life Sciences - March 21, 2019 Category: Biology Source Type: research

Mucin 1 downregulation impairs the anti-necroptotic effects of glucocorticoids in human bronchial epithelial cells
Publication date: Available online 7 February 2019Source: Life SciencesAuthor(s): Huojun Zhang, Qian Liu, Luxia Kong, Shuyun XuAbstractAimsTo investigate whether mucin 1 (MUC1) downregulation reduced the sensitivity of tumor necrosis factor-alpha (TNF-α)-induced bronchial epithelial cells to glucocorticoid-mediated necroptosis and explore the underlying mechanisms.Main methodsThe human lung bronchial epithelial cell line (16HBE) was transfected with small interfering RNA (siRNA) against MUC1 and then stimulated by TNF-α, where some cells were pretreated with dexamethasone. Flow cytometry was performed to analyze necropto...
Source: Life Sciences - February 7, 2019 Category: Biology Source Type: research

Glucocorticoids regulate MiR-29c levels in vascular smooth muscle cells through transcriptional and epigenetic mechanisms
The objective of this study was to determine the underlying mechanism by which glucocorticoids (GCs) induce of miR-29c expression in vascular smooth muscle cells. Main methods QRT-PCR was used for miR-29c detection. Protein levels were determined by western blotting. Knockdown of SP1, DNMT1 and DNMT3A was achieved through transfection with their specific respective siRNAs. The effect of GCs on SP1 activity was determined by luciferase reporter assay and the methylation status in miR-29c promoter was detected by methylation specific PCR. CHIP assay was used to determine the binding ability of SP1 and glucocorticoid receptor...
Source: Life Sciences - August 12, 2017 Category: Biology Source Type: research

Effects of Zinc Transporter on Differentiation of Bone Marrow Mesenchymal Stem Cells to Osteoblasts.
Abstract The differentiation of bone marrow mesenchymal stem cells (MSCs) into osteoblasts is a crucial step during bone formation. However, the exact mechanisms regulating the early stages of osteogenic differentiation remain unknown. In the present study, we found that ZnT7, a member of the zinc transporter family SLC30A(ZnTs), was downregulated during dexamethasone-induced differentiation of rat MSCs into osteoblasts. Dexamethasone treatment resulted in significantly lower levels of ZnT7 compared with cocultured cells without dexamethasone. Differentiation was evaluated by measuring alkaline phosphatase (ALP) a...
Source: Biological Trace Element Research - June 18, 2013 Category: Biology Authors: Liu Y, Yan F, Yang WL, Lu XF, Wang WB Tags: Biol Trace Elem Res Source Type: research