4-Phenyl butyric acid prevents glucocorticoid-induced osteoblast apoptosis by attenuating endoplasmic reticulum stress

Yang, Jianhui; Wu, Qiong; Lv, Jian-guo; Nie, Huiyong

doi:10.1007/s00774-016-0778-3

Cited by 24 publications

(16 citation statements)

References 37 publications

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“…Disrupting this balance has certain harmful effects; for instance, an increased production of ROS may inhibit the differentiation of osteoblasts ( 24 , 37 ). The results of the present study indicated that ER stress was activated by DEX via increasing the expression of the associated proteins ATF4 and CHOP, which is in accordance with the study by Yang et al ( 30 ). In addition, the results of the autophagy analysis indicated that DEX caused autophagy by increasing the levels of Beclin1 and LC3BII, and by decreasing the expression of P62.…”

Section: Discussionsupporting

confidence: 93%

“…ER stress is a state in which the homeostasis of protein folding load and the capacity of the ER is disrupted ( 28 , 29 ). Excess ER stress has been demonstrated in MC3T3-E1 cells after treatment with DEX, and has also been proven to induce apoptosis ( 30 , 31 ). Autophagy is known to be a self-degradative process that is important for balancing sources of energy at critical times during development, and in response to nutrient stress ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

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Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells

Liu

Zhao

et al. 2018

Int J Mol Med

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Apoptosis of osteoblasts, triggered by prolonged or excessive use of glucocorticoids (GCs), has been identified as a dominant contributor to the development of osteoporosis and osteonecrosis. However, the molecular mechanisms underlying GC-induced apoptosis are multifaceted and remain to be fully elucidated. The present study aimed to explore the correlation between dexamethasone (DEX)-induced reactive oxygen species (ROS), autophagy and apoptosis in MC3T3-E1 osteoblast-like cells. Cell viability was assessed using a Cell Counting Kit-8 assay, and flow cytometry was performed to assess cellular apoptosis, cell cycle and ROS production. Immunofluorescence and western blot analysis were respectively used to detect autophagic vacuoles and the expression of proteins, including cyclin D kinase (CDK)2, poly[ADP ribose] polymerase, caspase-3, activating transcription factor (ATF)4, CCAAT/enhancer-binding protein homologous protein (CHOP), Beclin1, microtubule-associated proteins 1A/1B light chain (LC)3B and P62. It was revealed that DEX not only reduced cell viability, but also promoted apoptosis via the activation of endoplasmic reticulum (ER) stress. In addition, DEX induced cell cycle arrest at G0/G1 phase via inhibition of the expression of CDK2, and the production of ROS was activated. Of note, the DEX-mediated changes in viability and apoptosis were attenuated in MC3T3-E1 cells after treatment with 3-methyladenine, which is an autophagy inhibitor. Treatment with the antioxidant N-acetylcysteine abolished the effect of DEX on the proliferation, apoptosis, ER stress and autophagy of MC3T3-E1 cells. In conclusion, the present results indicated that DEX promoted the production of ROS, which enhanced apoptosis through activation of autophagy and ER stress in MC3T3-E1 cells.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells

Liu

Zhao

et al. 2018

Int J Mol Med

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“…Release of cytochrome-C, an apoptogenic protein, by activated mitochondria into the cytosol triggers caspase proteases that degrade cells via the mitochondrial pathway [ 3 , 22 , 23 ]. Bax is a key regulator of the mitochondrial pathway of apoptosis that accumulates at distinct foci on the mitochondrial surface to undergo a conformational change, oligomerize, and mediate cytochrome-C translocation [ 24 ]. AIF induces caspase-independent fragmentation of chromosomal DNA to amplify apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Gastrodin alleviates glucocorticoid induced osteoporosis in rats via activating the Nrf2 signaling pathways

et al. 2018

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BackgroundProlonged and over-dosed administration of glucocorticoids results in more bone remodeling, leading to glucocorticoid-induced osteoporosis, which is primarily due to dysfunction and apoptosis of osteoblasts. The present study investigated the therapeutic effect and molecular mechanism of gastrodin, a natural bioactive compound isolated from the traditional Chinese herbal agent Gastrodia elata, on osteoblastic cells in vivo and in vitro.Materials and MethodsThe anti-dexamethasone (DEX) effects of gastrodin on primary osteoblasts were measured by cell viability, flow cytometry, and western blot analysis in vitro, and also extensively examined in a rat model in vivo.ResultsThe results show that gastrodin pretreatment significantly increased osteoblast viability and alkaline phosphatase activity when exposed to DEX. Alizarin Red staining indicated more calcium deposits formed in the gastrodin pretreatment against DEX group. Gastrodin alleviated DEX-induced reactive oxygen species at both the mitochondrial and cellular levels in osteoblasts. In addition, gastrodin protected primary osteoblasts from caspase3-related apoptosis by reducing the loss in the mitochondrial membrane potential and decreasing the release of DEX-induced cytochrome-C, bax, and apoptosis inducing factor. Gastrodin also antagonized upregulated endoplasmic reticulum stress signals induced by DEX, including the expression of GRP78, CHOP, and phosphorylated eIF2α. Furthermore, gastrodin protected osteoblasts by activating the nuclear factor erythroid derived 2-related factor-2 (Nrf2) pathway. Furthermore, femoral micro-computed tomography scans and biomechanical tests revealed that gastrodin improved bone microstructure and mitigated DEX-induced deterioration in bone quality.ConclusionsThese findings suggest that gastrodin alleviated glucocorticoid-induced osteoporosis in rats by protecting osteoblasts via the Nrf2 regulated mitochondrial and ER stress-related signaling pathways.

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“…Although ER stress correlates with various diseases, the role of ER stress in the pathogenesis of GC-induced ONFH remains unclear. A few studies have indicated that treatment with GCs leads to ER stress and results in various changes, including dysfunction and apoptosis of osteoblasts, osteocytes, and trabecular-meshwork cells (34,44,45). Nevertheless, few studies have focused on the GC-induced EC apoptosis mediated by the ER stress signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of PERK Signaling Prevents Against Glucocorticoid-induced Endotheliocyte Apoptosis and Osteonecrosis of the Femoral Head

Gao¹,

Zhu²,

Wang³

et al. 2020

Int. J. Biol. Sci.

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Vascular injury is considered an important pathological process during glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). In this study, we tried to investigate whether the endoplasmic reticulum (ER) stress is triggered in the GC-induced endotheliocyte (EC) apoptosis and ONFH. The results showed that a GC upregulated the expression of ER stress-related proteins, and PERK-CHOP signaling played an important role and induced EC apoptosis. The inhibition of PERK by GSK2656157 significantly decreased the GC-induced EC apoptosis in vitro and in vivo, thus protecting a rat model from vascular injury and significantly preventing GC-induced ONFH.

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4-Phenyl butyric acid prevents glucocorticoid-induced osteoblast apoptosis by attenuating endoplasmic reticulum stress

Cited by 24 publications

References 37 publications

Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells

Dexamethasone-induced production of reactive oxygen species promotes apoptosis via endoplasmic reticulum stress and autophagy in MC3T3-E1 cells

Gastrodin alleviates glucocorticoid induced osteoporosis in rats via activating the Nrf2 signaling pathways

Inhibition of PERK Signaling Prevents Against Glucocorticoid-induced Endotheliocyte Apoptosis and Osteonecrosis of the Femoral Head

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