Title |
DJ-1 controls bone homeostasis through the regulation of osteoclast differentiation
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Published in |
Nature Communications, November 2017
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DOI | 10.1038/s41467-017-01527-y |
Pubmed ID | |
Authors |
Hyuk Soon Kim, Seung Taek Nam, Se Hwan Mun, Sun-Kyeong Lee, Hyun Woo Kim, Young Hwan Park, Bokyung Kim, Kyung-Jong Won, Hae-Rim Kim, Yeong-Min Park, Hyung Sik Kim, Michael A. Beaven, Young Mi Kim, Wahn Soo Choi |
Abstract |
Receptor activator of NF-kB ligand (RANKL) generates intracellular reactive oxygen species (ROS), which increase RANKL-mediated signaling in osteoclast (OC) precursor bone marrow macrophages (BMMs). Here we show that a ROS scavenging protein DJ-1 negatively regulates RANKL-driven OC differentiation, also called osteoclastogenesis. DJ-1 ablation in mice leads to a decreased bone volume and an increase in OC numbers. In vitro, the activation of RANK-dependent signals is enhanced in DJ-1-deficient BMMs as compared to wild-type BMMs. DJ-1 suppresses the activation of both RANK-TRAF6 and RANK-FcRγ/Syk signaling pathways because of activation of Src homology region 2 domain-containing phosphatase-1, which is inhibited by ROS. Ablation of DJ-1 in mouse models of arthritis and RANKL-induced bone disease leads to an increase in the number of OCs, and exacerbation of bone damage. Overall, our results suggest that DJ-1 plays a role in bone homeostasis in normal physiology and in bone-associated pathology by negatively regulating osteoclastogenesis. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Belgium | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Scientists | 1 | 50% |
Members of the public | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 54 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 10 | 19% |
Student > Master | 7 | 13% |
Researcher | 4 | 7% |
Student > Bachelor | 3 | 6% |
Student > Doctoral Student | 3 | 6% |
Other | 7 | 13% |
Unknown | 20 | 37% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 11 | 20% |
Medicine and Dentistry | 9 | 17% |
Immunology and Microbiology | 4 | 7% |
Agricultural and Biological Sciences | 3 | 6% |
Neuroscience | 2 | 4% |
Other | 5 | 9% |
Unknown | 20 | 37% |