Excessive Production of Mitochondrion‑derived Reactive Oxygen Species Induced by Titanium Ions Leads to Autophagic Cell Death of Osteoblasts Via the SIRT3/SOD2 Pathway

Overview

Journal Mol Med Rep

Specialty Molecular Biology

Date 2020 May 30

PMID 32468046

Citations 12

Authors

Siqian Wang

Jingyuan Yang

Tingting Lin

Shengbing Huang

Jianfeng Ma

Xin Xu

Affiliations

Soon will be listed here.

Abstract

The incidence of peri-implant bone loss is high, and is a difficult condition to treat. Previous studies have shown that titanium (Ti) ions released from implants can lead to osteoblast cell damage, but the specific mechanisms have not been elucidated. The present study established a Ti ion damage osteoblast cell model. The levels of mitochondrion‑derived reactive oxygen species (mROS) and autophagy, cell viability and the sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) pathway were examined in this model. It was found that Ti ions decreased osteoblast viability. Moreover, with increased Ti ion concentration, the expression levels of microtubule associated protein 1 light chain 3α (LC3) progressively increased, P62 decreased, autophagic flow increased and mROS levels increased. After the addition of an autophagy inhibitor Bafilomycin A1 and Mito‑TEMPO, a mitochondrial antioxidant, the production of mROS was inhibited, the level of autophagy was decreased and cell activity was improved. In addition, with increased Ti ion concentration, the activity of SOD2 decreased, the acetylation level of SOD2 increased, the SIRT3 mRNA and protein expression levels decreased, and the activity of SIRT3 was significantly decreased. Furthermore, it was demonstrated that SIRT3 overexpression reduced the acetylation of SOD2 and increased the activity of SOD2, as well as reducing the production of mROS and the expression level of LC3, thus increasing cell viability. Therefore, the present results suggested that excessive production of mROS induced by Ti ions led to autophagic cell death of osteoblasts, which is dependent on the SIRT3/SOD2 pathway.

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