19 February 2020 : Laboratory Research
miRNA-411 Regulates Chondrocyte Autophagy in Osteoarthritis by Targeting Hypoxia-Inducible Factor 1 alpha (HIF-1α)
Fei Yang1ABCDEF, Rong Huang2ABCD, Hui Ma1BC, Xiaowei Zhao1EF*, Guodong Wang1ACEGDOI: 10.12659/MSM.921155
Med Sci Monit 2020; 26:e921155
Abstract
BACKGROUND: Osteoarthritis (OA) is the most common joint disease and is characterized by the progressive degeneration of articular cartilage. The molecular basis of OA involves various factors and has not been fully clarified. Autophagy is a conserved catabolic process that involves cellular degradation through the lysosomal machinery.
MATERIAL AND METHODS: We found that miRNA-411 regulates chondrocyte autophagy in OA by targeting hypoxia-inducible factor 1 alpha (HIF-1α) and identified the related molecular mechanism. OA condition in chondrocyte C28/I2 cells was induced by treatment with interleukin 1 beta (IL-1β). The protein expressions of LC3, p62, HIF-1α, ULK-1, and Beclin-1 were assessed by Western blot analysis, and LC3 expression was assessed by immunofluorescence.
RESULTS: TargetScan analysis showed that HIF-1α mRNA is directly targeted by miR-411, which was confirmed by luciferase reporter assay. miR-411 mimic decreased HIF-1α levels in chondrocytes while miR-411 inhibitor increased HIF-1α levels in chondrocytes. Furthermore, expression of LC3, ULK-1, P62, and Beclin-1 in chondrocytes was induced by miR-411 inhibitor and was downregulated by miR-411 mimics. In addition, miR-411 mimics reduced the expression level of LC3, as determined by immunofluorescence analysis.
CONCLUSIONS: Our results demonstrate that miR-411 promotes chondrocyte autophagy by targeting HIF-1α, suggesting that regulating HIF-1α by miR-411 might be a therapeutic strategy for OA.
Keywords: Hypoxia-Inducible Factor-Proline Dioxygenases, Osteoarthritis, Base Sequence, Cell Line, Chondrocytes, Hypoxia-Inducible Factor 1, alpha Subunit
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