miR-4262 regulates chondrocyte viability, apoptosis, autophagy by targeting SIRT1 and activating PI3K/AKT/mTOR signaling pathway in rats with osteoarthritis

Sun,Wencai; Li,Yintai; Wei,Suizhuan

doi:10.3892/etm.2017.5444

miR-4262 regulates chondrocyte viability, apoptosis, autophagy by targeting SIRT1 and activating PI3K/AKT/mTOR signaling pathway in rats with osteoarthritis

Authors:
- Wencai Sun
- Yintai Li
- Suizhuan Wei
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Affiliations: Department of Orthopaedics, The Third Hospital Affiliated to Qiqihar Medical College, Qiqihar, Heilongjiang 161006, P.R. China, Department of Rehabilitation, Baoji Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721000, P.R. China, Department of Orthopaedics, Baoji Traditional Chinese Medicine Hospital, Baoji, Shaanxi 721000, P.R. China
Published online on: November 6, 2017 https://doi.org/10.3892/etm.2017.5444
Pages: 1119-1128

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Abstract

The present study aimed to investigate the effect and underlying mechanism of microRNA (miR)‑4262 in the development of osteoarthritis (OA) in rats. Primary chondrocytes were separated from Sprague‑Dawley rats and then treated with tumor necrosis factor‑α (TNF‑α). The level of miR‑4262 was detected in TNF‑α‑treated chondrocytes, and then the miR‑4262 or its target gene sirtuin type 1 (SIRT1) level was overexpressed, or knocked down. Furthermore, cell viability, cell apoptosis, cell autophagy and matrix synthesis, as well as the expressions of proteins associated with the phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were detected. miR‑4262 was significantly overexpressed in TNF‑α‑treated chondrocytes compared with untreated cells (P<0.05). TNF‑α treatment or miR‑4262 overexpression significantly decreased cell viability, autophagy‑related proteins levels and matrix synthesis‑related proteins levels, as well as increased the apoptotic rate in chondrocytes (P<0.05). Overexpression of SIRT1 significantly increased cell viability, autophagy‑related proteins levels and matrix synthesis‑related proteins levels, as well as decreased the apoptotic rate in TNF‑α‑treated chondrocytes (P<0.05). In addition, the effects of miR‑4262 on cell viability, cell apoptosis, cell autophagy and matrix synthesis were inhibited by SIRT1 (P<0.05). Furthermore, upregulated miR‑4262 remarkably increased the expressions of phosphorylated (p)‑PI3K, p‑AKT and p‑mTOR (P<0.05) in TNF‑α treated chondrocytes. The present study revealed that the upregulation of miR‑4262 may promote the occurrence and development of OA in rats by regulating cell viability, cell apoptosis, cell autophagy, and matrix synthesis. Furthermore, these roles of miR‑4262 may be associated with PI3K/AKT/mTOR signaling pathway.

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