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抗氧化酶Prdx1通过抑制ROS和NFATc1信号通路来抑制破骨细胞生成。

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

作者信息

Wang Chao, Wang Gang, Song Fangming, Zhao Jinmin, Liu Qian, Xu Jiake

机构信息

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

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

出版信息

J Cell Physiol. 2024 Dec;239(12):e31431. doi: 10.1002/jcp.31431. Epub 2024 Sep 12.

DOI:10.1002/jcp.31431
PMID:39263840
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11649962/
Abstract

Bone 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.

摘要

骨骼是一个动态器官，在人的一生中不断进行重塑。细胞产生活性氧（ROS）对于调节骨稳态至关重要。破骨细胞是从巨噬细胞谱系分化而来的多核巨细胞，负责与ROS信号通路密切相关的溶骨性骨病。在本研究中，发现一种抗ROS酶——过氧化物还原酶1（Prdx1）在骨髓巨噬细胞和破骨细胞中均有表达。发现重组Prdx1蛋白可剂量依赖性地抑制ROS产生和破骨细胞分化。从机制上讲，Prdx1蛋白还减弱了NFATc1的激活以及C-Fos、V-ATPase-d2、组织蛋白酶K和整合素αV的表达。总体而言，Prdx1通过抑制RANKL介导的ROS活性，是破骨细胞形成的负调节因子，因此提示其在治疗破骨细胞相关疾病方面的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/f98193bb4ac7/JCP-239-0-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/aeb6dfb52a8f/JCP-239-0-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/fe6902a1284b/JCP-239-0-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/4c7853e9ec03/JCP-239-0-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/b4b458a645e6/JCP-239-0-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/1a88011b0c40/JCP-239-0-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/f98193bb4ac7/JCP-239-0-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/aeb6dfb52a8f/JCP-239-0-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/fe6902a1284b/JCP-239-0-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/12ac7d0e06d3/JCP-239-0-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/4c7853e9ec03/JCP-239-0-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/b4b458a645e6/JCP-239-0-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/1a88011b0c40/JCP-239-0-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5680/11649962/f98193bb4ac7/JCP-239-0-g001.jpg

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J Biol Chem. 2023 Feb;299(2):102889. doi: 10.1016/j.jbc.2023.102889. Epub 2023 Jan 9.
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A missense mutation sheds light on a novel structure-function relationship of RANKL.一个错义突变揭示了 RANKL 的一种新的结构-功能关系。
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Hymenialdisine: A Marine Natural Product That Acts on Both Osteoblasts and Osteoclasts and Prevents Estrogen-Dependent Bone Loss in Mice.
膜盘菌素：一种作用于成骨细胞和破骨细胞并预防小鼠雌激素依赖性骨质流失的海洋天然产物。
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