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

作者：Kim Hyuk Soon; Nam Seung Taek; Mun Se Hwan; Lee Sun Kyeong; Kim Hyun Woo; Park Young Hwan; Kim Bokyung; Won Kyung Jong; Kim Hae Rim; Park Yeong Min; Kim Hyung Sik; Beaven Michael A; Kim Young Mi; Choi Wahn Soo

来源：Nature Communications, 2017, 8(1): 1519.

DOI：10.1038/s41467-017-01527-y

<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

• 出版日期2017-11-15