Antioxidant enzyme Prdx1 inhibits osteoclastogenesis via suppressing ROS and NFATc1 signaling pathways

Author:

Wang Chao1,Wang Gang12ORCID,Song Fangming3,Zhao Jinmin3,Liu Qian3ORCID,Xu Jiake12ORCID

Affiliation:

1. The Discipline of Pathology and Laboratory, School of Biomedical Sciences The University of Western Australia Perth Western Australia Australia

2. Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology Chinese Academy of Sciences Shenzhen China

3. Guangxi Key Laboratory of Regenerative Medicine Guangxi Medical University Nanning Guangxi China

Abstract

AbstractBone is a dynamic organ which continuously undergoes remodeling throughout one's lifetime. Cellular production of reactive oxygen species (ROS) is essential for regulating bone homeostasis. Osteoclasts, multinucleated giant cells differentiated from macrophage lineage, are responsible for osteolytic bone conditions which are closely linked to ROS signaling pathways. In this study, an anti‐ROS enzyme, peroxiredoxin 1 (Prdx1) was found to be expressed both in bone marrow macrophages and osteoclasts. Recombinant Prdx1 protein was found to dose‐dependently inhibit ROS production and osteoclast differentiation. Mechanistically, Prdx1 protein also attenuated NFATc1 activation as well as the expression of C‐Fos, V‐ATPase‐d2, Cathepsin K, and Integrin αV. Collectively, Prdx1 is a negative regulator on osteoclast formation via inhibiting RANKL‐mediated ROS activity, thus suggesting its potential application for treating osteoclast related disorders.

Publisher

Wiley

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