CREB Ameliorates Osteoarthritis Progression Through Regulating Chondrocytes Autophagy via the miR-373/METTL3/TFEB Axis.

ABSTRACT: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation. Dysregulated autophagy is a major cause of OA. However, the underlying mechanism is unclear. Here, we found that the expression of element-binding protein (CREB) was downregulated in both cartilage tissues of OA patients and mouse OA model. In tert-butyl hydroperoxide solution-treated chondrocytes, increased apoptosis and autophagic blockage were attenuated by CREB overexpression. Mechanically, MiR-373 directly targeted the 3'UTR of methyltransferase-like 3 (METTL3) and led to its downregulation. METTL3 epigenetically suppressed TFEB. The upregulation of miR-373 by CREB overexpression induced the release of TFEB from METTL3 and restored the autophagy activity of chondrocytes. Taken togethe

SUBMITTER: Zhang H 

PROVIDER: S-EPMC9218638 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature