DJ-1 controls bone homeostasis through the regulation of osteoclast differentiation

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 and Wahn Soo Choi ()
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Hyuk Soon Kim: Konkuk University
Seung Taek Nam: Konkuk University
Se Hwan Mun: Konkuk University
Sun-Kyeong Lee: University of Connecticut Health Center, 263 Farmington Ave
Hyun Woo Kim: Konkuk University
Young Hwan Park: Konkuk University
Bokyung Kim: Konkuk University
Kyung-Jong Won: Konkuk University
Hae-Rim Kim: Konkuk University
Yeong-Min Park: Konkuk University
Hyung Sik Kim: Sungkyunkwan University
Michael A. Beaven: National Institutes of Health
Young Mi Kim: Duksung Women’s University
Wahn Soo Choi: Konkuk University

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01527-y

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