MiR-455-3p reduces apoptosis and alleviates degeneration of chondrocyte through regulating PI3K/AKT pathway

Abstract

Aims: This study aimed to explore the functions of miR-455-3p, PTEN, and PI3K/AKT pathway in osteoarthritis.

Materials and methods: We used the human bone marrow stem cell (BMSC), healthy chondrocytes, osteoarthritis chondrocytes (OA), and the IL-1β/TNF-α-treated chondrocyte model to explore the relationship between miR-455-3p and PTEN. Mimic or inhibitor was used to transfect chondrocytes to determine whether miR-455-3p can regulate PTEN and influence COL2A1 and MMP13. Apoptosis was detected by flow cytometry. A luciferase report was applied to verify the targeted binding. KO mice were applied to investigate PTEN and pAKT expression and the effect on chondrocytes in vivo.

Key findings: MiR-455-3p and PTEN were reverse in chondrogenesis and healthy cartilage versus OA cartilage. Similar trends were noted in IL-1β model. PTEN and MMP13 decreased and COL2A1 increased after overexpressing miR-455-3p, whereas the inhibition showed opposite results. Flow cytometry showed that miR-455-3p could reduce the apoptosis of chondrocytes. The results of luciferase revealed that miR-455-3p could affect fluorescence activity of PTEN by targeting its 3'-UTR. Finally, we found a marked increased in the expression of PTEN in KO mice relative to WT mice, while pAKT levels decreased.

Significance: It can be supported that miR-455-3p can reduce the apoptosis of chondrocytes and alleviate OA through regulating PI3K/AKT pathway, which may be expected to be a target for the treatment of osteoarthritis.

Keywords: Osteoarthritis; PI3K/AKT; PTEN; miR-455-3p.