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Positive programming of the GC-IGF1 axis mediates adult osteoporosis susceptibility in male offspring rats induced by prenatal dexamethasone exposure
In conclusion, PDE-induced intrauterine hypoglucocorticoid exposure could positively program IGF1 expression in bone tissue through the GRα/miR-130a-5p/HDAC4 pathways, thus mediating osteogenic dysdifferentiation and adult osteoporosis susceptibility in male offspring rats.PMID:36174767 | DOI:10.1016/j.bcp.2022.115264
Source: Biochemical Pharmacology - September 29, 2022 Category: Drugs & Pharmacology Authors: Yangfan Shangguan Xufeng Li Jun Qin Yinxian Wen Hui Wang Liaobin Chen Source Type: research

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

Decrease of GSK3 β Ser-9 Phosphorylation Induced Osteoblast Apoptosis in Rat Osteoarthritis Model
AbstractNowadays, the cumulative intake of glucocorticoids has become the most common pathogenic factor for non-traumatic osteonecrosis of the femoral head (ONFH). Apoptosis of osteoblasts is considered as the main reason of ONFH at the molecular level. Glycogen synthase kinase 3 β (GSK3β) is an important regulator of cellular differentiation and apoptosis pathway, which can modulate the balance between osteoblasts and osteoclasts. Several studies have reported about its function in osteoporosis, but little is known about it in osteonecrosis. In our study, lipopolysacchari de and methylprednisolone were utilized to estab...
Source: Journal of Huazhong University of Science and Technology -- Medical Sciences -- - January 31, 2019 Category: Research Source Type: research

Parathyroid hormone 1 ‑34 inhibits senescence in rat nucleus pulposus cells by activating autophagy via the m‑TOR pathway.
Parathyroid hormone 1‑34 inhibits senescence in rat nucleus pulposus cells by activating autophagy via the m‑TOR pathway. Mol Med Rep. 2018 Jun 27;: Authors: Wang XY, Jiao LY, He JL, Fu ZA, Guo RJ Abstract Osteoporosis is closely associated with intervertebral disc degeneration. While parathyroid hormone (PTH) 1‑34, which is an established drug used to treatosteoporosis, is thought to inhibit the disc degeneration associated with osteoporosis, the precise mechanism involved remains unclear. In the present study, primary Sprague‑Dawley rat nucleus pulposus cells (NPCs) were cultured, phenotyped...
Source: Molecular Medicine Reports - July 1, 2018 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Role of plasminogen activator inhibitor-1 in glucocorticoid-induced muscle change in mice
In conclusion, our data suggest that paracrine PAI-1 is involved in GC-induced muscle wasting through the enhancement of muscle degradation in mice.
Source: Journal of Bone and Mineral Metabolism - March 19, 2017 Category: Orthopaedics Source Type: research

FGF Suppresses Poldip2 Expression in Osteoblasts
This article is protected by copyright. All rights reserved
Source: Journal of Cellular Biochemistry - December 4, 2016 Category: Biochemistry Authors: Sakie Katsumura, Yayoi Izu, Takayuki Yamada, Kathy Griendling, Kiyoshi Harada, Masaki Noda, Yoichi Ezura Tags: Article Source Type: research

Indole-3-carbinol as inhibitors of glucocorticoid-induced apoptosis in osteoblastic cells through blocking ROS-mediated Nrf2 pathway.
In this study, we showed that, indole-3-carbinol (I3C), a natural product found in broadly consumed plants of the Brassica genus, could block the cytotoxic effects of dexamethasone (Dex), and elucidated the underlying molecular mechanisms. Firstly, we showed that, I3C could effectively suppress Dex-induced cytotoxicity and apoptotic cell death in osteoblastic cells, as evidenced by the decrease in Sub-G1 cell population. Treatment of the cells with Dex resulted in activation of caspase-3/-8/-9 and subsequent cleavage of PARP, which was also effectively blocked by co-incubation of I3C. Moreover, exposure to Dex triggered a ...
Source: Biochemical and Biophysical Research communications - March 17, 2015 Category: Biochemistry Authors: Lin H, Gao X, Chen G, Sun J, Chu J, Jing K, Li P, Zeng R, Wei B Tags: Biochem Biophys Res Commun Source Type: research

P53 Dependent Mitochondrial Permeability Transition Pore Opening Is Required for Dexamethasone‐Induced Death of Osteoblasts
Prolonged or overdose glucocorticoids (GCs) usage is the common cause of osteoporosis. In the present study, we studied the cellular mechanism of dexamethasone (Dex)‐induce osteoblast cell death by focusing on the role of mitochondrial permeability transition pore (mPTP). In cultured osteoblastic MC3T3‐E1 cells, Dex‐induced mPTP opening, which was demonstrated by mitochondrial membrane potential (MPP) decrease, cyclophilin‐D (CyPD)–adenine nucleotide translocator 1 (ANT‐1) mitochondrial complexation and cytochrome C (cyto‐C) release. The mPTP inhibitor sanglifehrin A (SfA) dramatically inhibited Dex‐induced...
Source: Journal of Cellular Physiology - February 25, 2014 Category: Cytology Authors: Yun‐fang Zhen, Guo‐dong Wang, Lun‐qing Zhu, Shi‐ping Tan, Fu‐yong Zhang, Xiao‐zhong Zhou, Xiao‐dong Wang Tags: Original Research Article Source Type: research