SIRT3/SOD2 Maintains Osteoblast Differentiation and Bone Formation by Regulating Mitochondrial Stress

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2017 Sep 16

PMID 28914882

Citations 133

Authors

Jing Gao

Zhihui Feng

Xueqiang Wang

Mengqi Zeng

Jing Liu

Shujun Han

Jie Xu

Lei Chen

Ke Cao

Jiangang Long

Zongfang Li

Weili Shen

Jiankang Liu

Affiliations

Soon will be listed here.

Abstract

Recent studies have revealed robust metabolic changes during cell differentiation. Mitochondria, the organelles where many vital metabolic reactions occur, may play an important role. Here, we report the involvement of SIRT3-regulated mitochondrial stress in osteoblast differentiation and bone formation. In both the osteoblast cell line MC3T3-E1 and primary calvarial osteoblasts, robust mitochondrial biogenesis and supercomplex formation were observed during differentiation, accompanied by increased ATP production and decreased mitochondrial stress. Inhibition of mitochondrial activity or an increase in mitochondrial superoxide production significantly suppressed osteoblast differentiation. During differentiation, SOD2 was specifically induced to eliminate excess mitochondrial superoxide and protein oxidation, whereas SIRT3 expression was increased to enhance SOD2 activity through deacetylation of K68. Both SOD2 and SIRT3 knockdown resulted in suppression of differentiation. Meanwhile, mice deficient in SIRT3 exhibited obvious osteopenia accompanied by osteoblast dysfunction, whereas overexpression of SOD2 or SIRT3 improved the differentiation capability of primary osteoblasts derived from SIRT3-deficient mice. These results suggest that SIRT3/SOD2 is required for regulating mitochondrial stress and plays a vital role in osteoblast differentiation and bone formation.

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