Hydroxytyrosol inhibits the inflammatory response of osteoarthritis chondrocytes via SIRT6-mediated autophagy

Zhi,Li‑Qiang; Yao,Shu‑Xin; Liu,Hong‑Liang; Li,Meng; Duan,Ning; Ma,Jian‑Bing

doi:10.3892/mmr.2017.8353

Hydroxytyrosol inhibits the inflammatory response of osteoarthritis chondrocytes via SIRT6-mediated autophagy

Authors:
- Li‑Qiang Zhi
- Shu‑Xin Yao
- Hong‑Liang Liu
- Meng Li
- Ning Duan
- Jian‑Bing Ma
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Affiliations: Department of Joint Surgery, Hong‑Hui Hospital, Xi'an Jiaotong University, Xi'an, Shanxi 710054, P.R. China, Department of Orthopaedic Trauma, Hong‑Hui Hospital, Xi'an Jiaotong University, Xi'an, Shanxi 710054, P.R. China, Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Traumatic Osteopathic, Hong‑Hui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, P.R. China
Published online on: December 27, 2017 https://doi.org/10.3892/mmr.2017.8353
Pages: 4035-4042

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Abstract

Osteoarthritis (OA) is a common degenerative joint disease. Inflammation may exaggerate the catabolism and degeneration in the pathogenesis of OA. Hydroxytyrosol (HT) has been used in the management of inflammatory diseases. In addition, reports have revealed that autophagy was a therapeutic target of diseases caused by inflammation. Sirtuin 6 (SIRT6) has also been demonstrated to prevent OA development by reducing both the inflammatory response and chondrocyte senescence. However, the roles of SIRT6 and autophagy in cartilage and its underlying anti‑inflammatory mechanism are unknown. Therefore, the present study aimed to determine the effects of HT on autophagy and inflammation in chondrocytes, and clarify whether HT regulates the inflammatory response through SIRT6‑mediated autophagy. The expression of protein and mRNA were determined by western blot analysis and reverse transcription‑quantitative polymerase chain reaction. The production of cytokines was detected by ELISA. It was demonstrated that HT inhibited the levels of interleukin (IL)‑1β and IL‑6 in tumor necrosis factor (TNF)‑α‑stimulated chondrocytes in a concentration‑dependent manner. In addition, HT promoted cell autophagy and increased the mRNA and protein expression levels of SIRT6 in chondrocytes stimulated with TNF-α. Autophagy inhibitor 3-methyladenine or knockdown of SIRT6 decreased the inhibitory effects of HT on the inflammatory response in chondrocytes. In addition, knockdown of SIRT6 attenuated the expression of microtubule-associated protein 1A/1B‑light chain 3 and Beclin1 in chondrocytes. Overall, these findings suggested that HT inhibits the inflammatory response of chondrocytes through SIRT6‑mediated autophagy. The present study provided a new drug target for the clinical treatment of inflammatory diseases.

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