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Regulation of the mesenchymal stem cell fate by interleukin-17: Implications in osteogenic differentiation

World Journal of Stem Cells 2021年第11期13卷 1696-1713页

作者： Jelena Krstić Slavko Mojsilović Sonja S Mojsilović juan f santibanez Gottfried Schatz Research Center Medical University of GrazGraz 8010Austria Group for Hematology and Stem Cells Institute for Medical ResearchNational Institute of Republic of SerbiaUniversity of BelgradeBelgrade 11129Serbia Group for Immunology Institute for Medical ResearchNational Institute of Republic of SerbiaBelgrade 11129Serbia Group for Molecular Oncology Institute for Medical ResearchNational Institute of Republic of SerbiaUniversity of BelgradeBelgrade 11000Serbia Centro Integrativo de Biología y Química Aplicada Universidad Bernardo O’HigginsChile 8370993Chile

Bone regeneration is a tightly regulated process that ensures proper repair and functionality after *** delicate balance between bone formation and resorption is governed by cytokines and signaling molecules released during the inflammatory ***(IL)-17A,produced in the early phase of inflammation,influences the fate of *** to their inherent capacity to differentiate into osteoblasts,mesenchymal stem/stromal cells(MSCs)contribute to bone healing and *** review presents an overview of IL-17A signaling and the leading cellular and molecular mechanisms by which it regulates the osteogenic differentiation of *** main findings demonstrating IL-17A’s influence on osteoblastogenesis are *** this end,divergent information exists about the capacity of IL-17A to regulate MSCs’osteogenic fate,depending on the tissue context and target cell type,along with contradictory findings in the same cell ***,we summarize the data showing both the pro-osteogenic and anti-osteogenic roles of IL-17,which may help in the understanding of IL-17A function in bone repair and regeneration.

关键词： Interleukin-17 Mesenchymal stem cells Osteoblast Bone Osteogenesis Inflammation

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Telmisartan induces melanoma cell apoptosis and synergizes with vemurafenib in vitro by altering cell bioenergetics

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Cancer Biology & Medicine 2019年第2期16卷 247-263页

作者： Jelena Grahovac Tatjana Srdic-Rajic juan francisco santibanez Marijana Pavlovic Milena Cavic Sinisa Radulovic1 Laboratory for Experimental Pharmacology Institute for Oncology and Radiology of Serbia Belgrade 11000 Serbia Department of Molecular Oncology Institute for Medical Research University of Belgrade Belgrade 11000 Serbia Integrative Center for Biology and Applied Chemistry (CIBQA) Bernardo O'Higgins University Santiago 8370854 Chile

Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents a serious challenge and new approaches for melanoma treatment are urgently needed. The objective of this study was to examine the effects of telmisartan, an AGTR1 inhibitor and a partial agonist of PPARγ, on melanoma cells as a potential agent for repurposing in melanoma ***: Expression of AGTR1 and PPARγ m RNA in melanoma patient tumor samples was examined in publicly available datasets and confirmed in melanoma cell lines by qRT-PCR. A panel of melanoma cell lines was tested in viability, apoptosis and metabolic assays in presence of telmisartan by flow cytometry and immunocytochemistry. A cytotoxic effect of combinations of telmisartan and targeted therapy vemurafenib was examined using the Chou-Talalay combination index ***: Both AGTR1 and PPARγ mRNA were expressed in melanoma patient tumor samples and decreased compared to the expression in the healthy skin. In vitro, we found that telmisartan decreased melanoma cell viability by inducing cell *** glucose uptake, but not utilization, in the presence of telmisartan caused the fission of mitochondria and release of reactive oxygen species. Telmisartan altered the cell bioenergetics, thereby synergizing with vemurafenib in vitro, and even sensitized vemurafenib-resistant cells to the ***: Given that the effective doses of telmisartan examined in our study can be administered to patients and that telmisartan is a widely used and safe antihypertensive drug, our findings provide the scientific rationale for testing its efficacy in treatment of melanoma progression.

关键词： Melanoma telmisartan apoptosis mitochondria reactive oxygen species targeted therapy

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