Project description:Due to the lack of a precise in vitro model that can mimic the nature microenvironment in osteosarcoma, the understanding of its resistance to chemical drugs remains limited. Here, we report a novel three-dimensional model of osteosarcoma constructed by seeding tumor cells (MG-63 and MNNG/HOS Cl #5) within in demineralized bone matrix scaffolds. Demineralized bone matrix scaffolds retain the original components of the natural bone matrix (hydroxyapatite and collagen type I), and possess good biocompatibility allowing osteosarcoma cells to proliferate and aggregate into clusters within the pores. Growing within the scaffold conferred elevated resistance to doxorubicin on MG-63 and MNNG/HOS Cl #5 cell lines as compared with two-dimensional cultures. Transcriptomic analysis showed an increased enrichment for drug resistance genes along with enhanced glutamine metabolism in osteosarcoma cells in demineralized bone matrix scaffolds. Inhibition of glutamine metabolism resulted a decrease in drug resistance of osteosarcoma, which could be restored by α-ketoglutarate supplementation. Overall, our study suggests that microenvironmental cues in demineralized bone matrix scaffolds can enhance osteosarcoma drug responses and that targeting glutamine metabolism may be a strategy for treating osteosarcoma drug resistance.
Project description:Asthma is a chronic inflammatory airway disease characterized by airway inflammation and remodeling. The role of 15-oxo-5Z,8Z,11Z,13E-eicosatetraenoic acid (15-oxoETE), a 15-HETE metabolite catalyzed by 15-prostaglandin dehydrogenase (15-PGDH), has been relatively unexplored in asthma. In this study, we used RNA-seq to explore the effect of 15-KETE on the transcriptome of airway epithelial cells, aiming to identify its potential downstream targets and mechanisms of action.
Project description:Osteosarcoma (OS) is the most prevalent primary malignant bone tumor.We have recently succeeded in generating CSC-like cells (MG-OKS) from the OS cell line MG-63 by transducing defined factors. A significant increase was observed in small proline-rich protein 1A (SPRR1A) expression, a cross-linked envelope protein in keratinocytes, in MG-OKS cells. This study aimed to evaluate the role of SPRR1A in OS using novel MG-OKS cells. MG-OKS cells were transfected with SPRR1A siRNA (siMG-OKS) to suppress SPRR1A expression selectively; MG-OKS and scrambled siRNA-transfected MG-OKS (scMG-OKS) cells served as controls. Our date that genes involved in cell adhesion were suppressed in the siMG-OKS group, suggesting that suppression of cell adhesion may cause phenotypic changes.
