MiR-27a promotes the autophagy and apoptosis of IL-1β treated-articular chondrocytes in osteoarthritis through PI3K/AKT/mTOR signaling

Abstract

Osteoarthritis (OA) is a common degenerative joint disorder, which involves articular cartilage degeneration as well as joint inflammatory reactions. The recent studies have identified microRNA (miRNA) as one of the epigenetic mechanisms for the regulation of gene expression. Here we aim to reveal the role of miRNA in the regulation of gene expression in articular chondrocytes and its significance in the OA pathogenesis. In the present study, miRNA profiling was performed using OA cartilage and normal healthy cartilage tissues. As compared to their levels in normal cells and tissues, miR-27a expression was found to be upregulated in OA cartilage and IL-1β-treated articular chondrocytes. TUNEL staining, as well as flow cytometry with Annexin V-FITC/PI double labeling indicated that miR-27a inhibition reduced the apoptosis of IL-1β-treated articular chondrocytes. Bioinformatics prediction and the dual-luciferase reporter assay indicated that miR-27a targeted the 3′-UTR of the PI3K gene to silence it. The PI3K mRNA level in OA cartilage and IL-1β-treated articular chondrocytes was also downregulated, comparing with normal cells and tissues. Transfection of chondrocytes transfected with the miR-27a inhibitor upregulated the PI3K expression. This study demonstrated miR-27a is a regulator of the PI3K-Akt-mTOR axis in human chondrocytes and could participate in OA pathogenesis.

hBMSC-Derived Extracellular Vesicles Attenuate IL-1β-Induced Catabolic Effects on OA-Chondrocytes by Regulating Pro-inflammatory Signaling Pathways

“…Accumulating evidence demonstrated that pro-inflammatory cytokines, such as IL-1β, TNF, and IL-6, are involved in the pathophysiology of OA (Robinson et al, 2016;Philpott et al, 2017;Urban and Little, 2018). Especially, IL-1β can act as an independent pro-inflammatory cytokine alone in promoting the progression of OA by inducing chondrocyte apoptosis and proinflammatory signaling via MAPK, NF-κB, mTOR, and PI3K/Akt signaling pathways (Moon et al, 2018;Cai et al, 2019;Zhou et al, 2019). Several reports have shown that BMSC-derived EVs play an anti-inflammatory role in OA pathophysiology through regulating MAPK, NF-κB, mTOR, and PI3K/Akt signaling pathways (Zhao et al, 2018;Sun et al, 2019;Xia et al, 2019;Zhu et al, 2019).…”

ANXA6 Contributes to Radioresistance by Promoting Autophagy via Inhibiting the PI3K/AKT/mTOR Signaling Pathway in Nasopharyngeal Carcinoma

“…Inhibition of the PI3K/AKT/mTOR signaling pathway is one of the classical pathways for autophagy induction. There is increasing evidence showing that the activation of autophagy associated with the inhibition of the PI3K/AKT/mTOR pathway regulates many biological processes, including platelet activation, psoriasis regulation, and osteoarthritis attenuation (Varshney and Saini, 2018;Wang et al, 2018;Cai et al, 2019). However, few studies have focused on the role of autophagy induced by PI3K/AKT/mTOR inhibition in the radioresistance of NPC.…”

Oleanolic acid mitigates interleukin‐1β‐induced chondrocyte dysfunction by regulating miR‐148‐3p‐modulated FGF2 expression

“…Previous studies have reported that chondrocyte apoptosis plays a critical role in cartilage degeneration, which is associated with the etiology of OA . Therefore, the anti‐apoptotic role of OLA is must be determined in chondrocytes.…”