Dexamethasone induces osteoblast apoptosis through ROS-PI3K/AKT/GSK3β signaling pathway

Deng, Shuang; Dai, Guo; Chen, Sen; Nie, Zhigang; Zhou, Jianlin; Fang, Hongsong; Peng, Hao

doi:10.1016/j.biopha.2018.11.103

Cited by 158 publications

(100 citation statements)

References 32 publications

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“…In addition, the inactivation of GSK 3β has also been revealed to suppress cell apoptosis in pre-invasive and invasive OSCC ( 51 , 53 , 54 ). Furthermore, as the induction of intracellular reactive oxygen species (ROS) stimulates cell apoptosis ( 55 ), constitutively activated GSK 3β has been reported to increase the mitochondrial membrane potential and to promote ROS ( 56 , 57 ). In addition, several matrix metalloproteinases (MMPs) can also facilitate the migration of cancer cells, thereby upregulating and activating tumor factors, such as Snail, AP-1 and NF-κB in OSCC ( 58 , 59 ).…”

Section: Role Of Gsk 3β In Tumorigenesismentioning

confidence: 99%

Glycogen synthase kinase 3β in tumorigenesis and oncotherapy (Review)

Lei³

et al. 2020

Oncol Rep

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Glycogen synthase kinase 3β (GSK 3β), a multifunctional serine and threonine kinase, plays a critical role in a variety of cellular activities, including signaling transduction, protein and glycogen metabolism, cell proliferation, cell differentiation, and apoptosis. Therefore, aberrant regulation of GSK 3β results in a broad range of human diseases, such as tumors, diabetes, inflammation and neurodegenerative diseases. Accumulating evidence has suggested that GSK 3β is correlated with tumorigenesis and progression. However, GSK 3β is controversial due to its bifacial roles of tumor suppression and activation. In addition, overexpression of GSK 3β is involved in tumor growth, whereas it contributes to the cell sensitivity to chemotherapy. However, the underlying regulatory mechanisms of GSK 3β in tumorigenesis remain obscure and require further in-depth investigation. In this review, we comprehensively summarize the roles of GSK 3β in tumorigenesis and oncotherapy, and focus on its potentials as an available target in oncotherapy.

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Section: Role Of Gsk 3β In Tumorigenesismentioning

confidence: 99%

Glycogen synthase kinase 3β in tumorigenesis and oncotherapy (Review)

Lei³

et al. 2020

Oncol Rep

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“…The mesenchymal stem cells apoptosis and the subsequent reduction of bone formation is the direct cause of osteonecrosis (Deng et al, 2018) (Pilsl & Winklhofer, 2012). The mitochondrial dysfunction plays important roles in the progression of GIOFH (Tsuchiya et al, 2018).…”

Section: F I G U R Ementioning

confidence: 99%

Desferoxamine protects against glucocorticoid‐induced osteonecrosis of the femoral head via activating HIF‐1α expression

Jing

Yang

et al. 2020

Journal Cellular Physiology

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Glucocorticoid‐induced osteonecrosis of the femoral head (GIOFH) is one of the most common complications of glucocorticoid administration. By chelating Fe2+, desferoxamine (DFO) was reported to be able to activate the HIF‐1α/VEGF pathway and promote angiogenesis. In the present study, we examined whether DFO administration could promote angiogenesis and bone repair in GIOFH. GIOFH was induced in rats by methylprednisolone in combination with lipopolysaccharide. Bone repair was assessed by histologic analysis and microcomputed tomography (micro‐CT). Vascularization was assessed by Microfil perfusion and micro‐CT analysis. Immunohistochemical staining was performed to analyze the expression of HIF‐1α, VEGF, and CD31. Our in vivo study revealed that DFO increased HIF‐1α/VEGF expression and promoted angiogenesis and osteogenesis in GIOFH. Moreover, our in vitro study revealed that DFO restored dexamethone‐induced HIF‐1α downregulation and angiogenesis inhibition. Besides, our in vitro study also demonstrated that DFO could protect bone marrow‐derived stem cells from dexamethone‐induced apoptosis and mitochondrial dysfunction by promoting mitophagy and mitochondrial fission. In summary, our data provided useful information for the development of novel therapeutics for management of GIOFH.

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“…Based on the results of biological functional analysis, there are a variety of pathways like PI3K-Akt signaling pathway, MAPK signaling pathway, FoxO signaling pathway [44], Ras signaling pathway [45] and Endocrine resistance [46], are robustly correlated with the pathogenesis of CHD. Interestingly, the PI3K-AKT signaling pathway has been reported to participate in the signal transduction that related to various cell activities such as proliferation, differentiation and apoptosis [47]. demonstrated that the up-regulation of Bcl2 expression in PI3K-Akt pathway can effectively protect the injury caused by ischemia and hypoxia [50].…”

Section: Functional Analysis Of Candidate Targetsmentioning

confidence: 99%

Investigating the pharmacological mechanisms of SheXiang XinTongNing against coronary heart disease based on network pharmacology

Jia

Cao³

et al. 2020

Preprint

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Background SheXiang XinTongNing, a commercially available Chinese patent medicine, has been widely used in the treatment of coronary heart disease. However, the mechanisms of SheXiang XinTongNing are still unclear. The aim of this study was to investigate the pharmacological mechanisms of SheXiang XinTongNing against coronary heart disease via network analysis. Method The traditional Chinese medicine system pharmacology analysis platform was used to screen the potential active constituents of the six traditional Chinese medicines in SheXiang XinTongNing, and the potential targets were obtained from PharmMapper. The genome annotation database platform was used to screen the candidate targets related to coronary heart disease. Then the drug-components-targets network and protein interaction network were built by Cytoscape 3.6.0 software. Further, GO bio-functional enrichment analysis and KEGG pathway enrichment analysis were performed through annotation, visualization and integrated discovery database. Results Results showed that the drugs-components-targets network contains 104 targets and 62 key components. The protein interaction network consisted of 107 nodes; key targets included Bcl2l1, IGF1, SRC, CASP3, et al. Functionally, the candidate targets were significantly associated with multiple pathways such as PI3K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, FoxO signaling pathway, Endocrine resistance. Given the above, the pharmacological activities of SheXiang XinTongNing may be predominantly related to several factors such as cell apoptosis, inflammation and angiogenesis. Conclusion XTN can effectively attenuate the symptoms of coronary heart disease through diverse pathways. The research proves that network pharmacology can successfully reveal the mechanisms of traditional Chinese medicine in a holistic view. Our systematic analysis lays a foundation for further studying.

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Dexamethasone induces osteoblast apoptosis through ROS-PI3K/AKT/GSK3β signaling pathway

Cited by 158 publications

References 32 publications

Glycogen synthase kinase 3β in tumorigenesis and oncotherapy (Review)

Glycogen synthase kinase 3β in tumorigenesis and oncotherapy (Review)

Desferoxamine protects against glucocorticoid‐induced osteonecrosis of the femoral head via activating HIF‐1α expression

Investigating the pharmacological mechanisms of SheXiang XinTongNing against coronary heart disease based on network pharmacology

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