First Author | Kim HS | Year | 2017 |
Journal | Nat Commun | Volume | 8 |
Issue | 1 | Pages | 1519 |
PubMed ID | 29142196 | Mgi Jnum | J:255920 |
Mgi Id | MGI:6106353 | Doi | 10.1038/s41467-017-01527-y |
Citation | Kim HS, et al. (2017) DJ-1 controls bone homeostasis through the regulation of osteoclast differentiation. Nat Commun 8(1):1519 |
abstractText | 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-FcRgamma/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. |