Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, Chrysanthemum zawadskii extract (CZE) was investigated to determine its effects on 2-deoxy-D-ribose (dRib)-induced oxidative damage and cellular dysfunction in the MC3T3-E1 mouse osteoblastic cell line. Osteoblastic cells were treated with the highly reducing sugar, dRib, in the presence or absence of CZE. Cell viability, apoptosis and reactive oxygen species (ROS) production were subsequently examined. It was observed that dRib reduced cell survival, while it markedly increased the intracellular levels of ROS and apoptosis. However, pre-treatment of the cells with CZE attenuated all the dRib-induced effects. The antioxidant, N-acetyl-L-cysteine (NAC), also prevented dRib-induced oxidative cell damage. In addition, treatment with CZE resulted in a significant increase in alkaline phosphatase (ALP) activity and collagen content, as well as in the expression of genes associated with osteoblast differentiation [ALP, collagen, osteopontin (OPN), osteoprotegerin (OPG), bone sialoprotein (BSP), osteocalcin (OC) and bone morphogenetic protein (BMP)2, BMP4 and BMP7]. In mechanistic studies of the antioxidative potential of CZE, we found that CZE reversed the dRib-induced decrease in the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT)1 and AKT2 genes, which are master regulators of survival-related signaling pathways. CZE also upregulated the gene expression of the antioxidant enzymes, superoxide dismutase (SOD)2, SOD3 and glutathione peroxidase 4 (GPx4), which was inhibited by dRib. Taken together, these results suggest that CZE attenuates dRib-induced cell damage in osteoblastic cells and may be useful for the treatment of diabetes-associated bone disease.
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PMID:Chrysanthemum zawadskii extract protects osteoblastic cells from highly reducing sugar-induced oxidative damage. 2365 75

Abnormal antioxidative capabilities were observed in the pathogenesis of steroid-induced osteoporosis (SIOP). Ferroptosis is a recently discovered type of cell death that is characterized by the overproduction of ROS in response to GPX4 and system Xc- downregulation, which is mediated by an Fe2+ fenton reaction. However, investigations focusing on the relationship between ferroptosis and steroid-induced bone disease remain limited. In the present study, high-dose dexamethasone was used to establish a mouse SIOP model, and extracellular vesicles extracted from bone marrow-derived endothelial progenitor cells (EPC-EVs) alleviated the pathological changes in SIOP via microtomography (micro-CT), with elevations in bone volume (BV), bone surface (BS), trabecular thickness (Tb.Th), and trabecular connectivity density (Conn-D) and decreases in trabecular separation (Tb.sp) and the structure model index (SMI). Histopathological analysis, such as haematoxylin and eosin (HE) and Masson staining, showed that EPC-EVs treatment increased the volume and density of the trabecular bone and bone marrow. RNA sequencing (RNA-seq) and bioinformatics analysis revealed subcellular biological alterations upon steroid and EPC-EVs treatment. Compared with the control, high-dose dexamethasone downregulated GPX4 and system XC-, and the Kyoto Encyclopedia of Genes and Genomes (KEGG)-based gene set enrichment analysis suggested that the ferroptotic pathway was activated. In contrast, combination treatment with EPC-EVs partly reversed the KEGG-mapped changes in the ferroptotic pathway at both the gene and mRNA expression levels. In addition, alterations in ferroptotic marker expression, such as SLC3A2, SLC7A11, and GPX4, were further confirmed by RNA-seq. EPC-EVs were able to reverse dexamethasone treatment-induced alterations in cysteine and several oxidative injury markers, such as malondialdehyde (MDA), glutathione (GSH), and glutathione disulphide (GSSG) (as detected by ELISA). In conclusion, EPC-EVs prevented mouse glucocorticoid-induced osteoporosis by suppressing the ferroptotic pathway in osteoblasts, which may provide a basis for novel therapies for SIOP in humans.
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PMID:Extracellular vesicles from endothelial progenitor cells prevent steroid-induced osteoporosis by suppressing the ferroptotic pathway in mouse osteoblasts based on bioinformatics evidence. 3169 92