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

Nat Commun 2017 11 15;8(1):1519. Epub 2017 Nov 15.

Department of Immunology and Physiology, School of Medicine, Konkuk University, Chungju, 380-701, Republic of Korea.

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.

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http://dx.doi.org/10.1038/s41467-017-01527-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688089PMC
November 2017
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