miR-31-5p/SOX4 Axis Affects Autophagy and Apoptosis of Chondrocytes by Regulating Extracellular Regulated Protein Kinase/Mechanical Target of Rapamycin Kinase Signalling.

Autor: Xu F; Department of Orthopedics, Affiliated Hospital of Chengde Medical College, Chengde, China., Lv YM; Department of Orthopedics, Affiliated Hospital of Chengde Medical College, Chengde, China., Wang HB; Department of Orthopedics, Tangshan Central Hospital, Tangshan, China., Song YC; Department of Anesthesiology, Affiliated Hospital of Chengde Medical College, Chengde, China.
Jazyk: angličtina
Zdroj: Pathobiology : journal of immunopathology, molecular and cellular biology [Pathobiology] 2022; Vol. 89 (2), pp. 63-73. Date of Electronic Publication: 2021 Nov 09.
DOI: 10.1159/000519006
Abstrakt: Background: Osteoarthritis (OA) is a common type of degenerative joint diseases that is regulated by a combination of complex intercellular signals and modulators, including non-coding RNAs. Mounting evidence suggests that miR-31-5p is physiologically involved in the regulation of chondrocytes, but the mechanism remains unclear.
Methods: Expression levels of miR-31-5p and SOX4 in OA cartilage tissues and in IL-1β-stimulated chondrocytes were examined by quantification polymerase chain reaction (q-PCR) or immunohistochemistry assays. Cell proliferation and apoptosis were detected by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. Expression of LC3 was detected using immunofluorescence staining. Expressions of autophagy-related proteins and extracellular regulated protein kinase (ERK)/mechanical target of rapamycin kinase (mTORC1) signal-related proteins were measured by Western blot analysis. Molecular interaction was validated by dual luciferase reporter assay.
Results: Downregulation of miR-31-5p and upregulation of SOX4 were observed in both OA patients and OA chondrocytes. Mechanistic experiments revealed that miR-31-5p negatively modulated SOX4 expression by directly targeting its 3'- untranslated region. Moreover, overexpression of miR-31-5p suppressed the activation of mTORC1 in an ERK-dependent manner by inhibiting SOX4. Further functional experiments demonstrated that overexpressing miR-31-5p in OA chondrocytes markedly promoted its proliferation and autophagy while inhibiting apoptosis. However, these effects were abolished by overexpression of SOX4 or treatment with 3BDO, an mTOR activator.
Conclusion: These results demonstrated that miR-31-5p enhanced survival and autophagy of OA chondrocytes through inactivation of mTORC1 via directly targeting SOX4, suggesting that miR-31-5p may play a protective role in OA progression.
(© 2021 S. Karger AG, Basel.)
Databáze: MEDLINE
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