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Τετάρτη 9 Δεκεμβρίου 2020

Tetrahedral Framework Nucleic Acid Inhibits Chondrocyte Apoptosis and Oxidative Stress through Activation of Autophagy.

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Tetrahedral Framework Nucleic Acid Inhibits Chondrocyte Apoptosis and Oxidative Stress through Activation of Autophagy.

ACS Appl Mater Interfaces. 2020 Dec 08;:

Authors: Shi S, Tian T, Li Y, Xiao D, Zhang T, Gong P, Lin Y

Abstract
Osteoarthritis (OA) is a degenerative articular cartilage pathogenic process that is accompanied by excessive chondrocyte apoptosis. The occurrence of chondrocyte death and OA is related to decreased autophagy. Tetrahedral framework nucleic acid (TFNA), a potent bioactive DNA nanomaterial, exerts antiapoptotic and antioxidative effects in various diseases, resulting in autophagy promotion and inhibition of the Wnt/β-catenin-signaling pathway. Here, we aimed to elucidate the therapeutic effects of TFNA on OA and its potential molecular mechanism of action. TFNA was synthesized and characterized by established methods. An interleukin (IL)-1β stimulated OA cell model was established and treated with TFNA. Cellular uptake of TFNA and intracellular reactive oxygen species levels were examined via immunofluorescence and flow cytometry. Apoptotic cell death was documented by the Cell Counting Kit-8 (CCK8) assay and flow cytometry. Transmission electron microscopy was applied to vi ew the autophagosomes. The expression of BCL2, BAX, caspase-3, Nrf2, HO-1, LC3-II, Beclin1, Atg7, β-catenin, Lef-1, and CyclinD1 was detected by immunofluorescence and western blotting. TFNA was successfully synthesized and effectively entered chondrocytes in the absence or presence of IL-1β without the help of transfection agents. TFNA treatment in IL-1β-induced chondrocytes reduced apoptosis by activating the BCL2/BAX/caspase-3 pathway, inhibited oxidative stress by regulating the Nrf2/HO-1-signaling pathway, and enhanced autophagy through upregulated LC3-II, Beclin1, and Atg7. Moreover, TFNA showed chondroprotective effects by regulating the Wnt/β-catenin-signaling pathway. Overall, TFNA may have utility as a therapeutic nanomedicine for OA.

PMID: 33289541 [PubMed - as supplied by publisher]

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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