TFEB, a potential therapeutic target for osteoarthritis via autophagy regulation.

Cell Death & Disease
Gang ZhengXiaolei Zhang

Abstract

The blockage of autophagic flux in chondrocytes has been considered as a major reason for the excessive cellular apoptosis and senescence in osteoarthritis (OA) development; however, the molecular mechanism and therapeutic strategy for interrupted autophagic flux is still not clear. Most recently, the transcription factor EB (TFEB) is identified as a master regulator for autophagic flux via initiating the expression of multiple autophagy-related genes and lysosomal biogenesis. This research was performed to confirm whether TFEB expression and activity are impacted in OA development and to confirm the effect of genetic up-regulation of TFEB on autophagic flux and cellular protection in the in vitro and in vivo models of OA. We demonstrated that the expression and nuclear localization of TFEB is decreased in human and mouse OA cartilage as well as in tert-Butyl hydroperoxide (TBHP)-treated chondrocytes. Applying lentivirus to transfect chondrocytes, we found that TFEB overexpression rescues the TBHP-induced the autophagic flux damage, lysosome dysfunction and protects chondrocyte against TBHP induced apoptosis and senescence; these protections of TFEB are diminished by chloroquine-medicated autophagy inhibition. Our destabilized ...Continue Reading

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Citations

Jun 28, 2020·Journal of Tissue Engineering and Regenerative Medicine·Junsong JiangXuehong Liu
Sep 18, 2020·Biology·Margot NeefjesPeter M van der Kraan
May 31, 2019·Human Genetics·Shi Q WongLouis R Lapierre
Jan 19, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Mingbao GuXiaolei Zhang
Feb 9, 2021·International Journal of Biological Macromolecules·Kai XuJiapeng Bao
Dec 17, 2020·Frontiers in Cell and Developmental Biology·Ran DuanZheng-Zhao Liu
Apr 4, 2021·International Journal of Molecular Sciences·Maria Teresa ValentiMonica Mottes
Sep 2, 2021·Journal of Inflammation Research·Yang SongBin Chen

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Methods Mentioned

BETA
nuclear translocation
transfection
ELISA
X-ray
PCR
protein assay
electrophoresis

Software Mentioned

SPSS
Adobe Photoshop
Image Lab
ImageJ
Image J

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