The Nuclear Receptor AhR Controls Bone Homeostasis by Regulating Osteoclast Differentiation via the RANK/c-Fos Signaling Axis.

摘要: The aryl hydrocarbon receptor (AhR) pathway plays a key role in activator of NF-κB ligand (RANKL)–mediated osteoclastogenesis. However, the mechanism underlying regulation AhR expression osteoclasts and signaling through which controls osteoclastogenesis remain unclear. We found that bone marrow–derived was upregulated by RANKL at an earlier stage than signature osteoclast genes such as those encoding cathepsin K NFAT, cytoplasmic, calcineurin-dependent 1. In response to RANKL, marrow macrophages isolated from AhR−/− mice exhibited impaired phosphorylation Akt MAPK well NF-κB, whereas their M-CSF remained unchanged. Osteoclast differentiation mediated also regulated RANKL/c-Fos–dependent manner. Furthermore, activation smoke toxin benzo[a]pyrene accelerated receptor-dependent manner, AhR-dependent mitochondrial biogenesis observed. Moreover, healing with delayed endochondral ossification. Taken together, present results suggest RANKL/AhR/c-Fos axis critical osteoclastogenesis, thereby identifying potential treating pathological, inflammatory, or metabolic disorders bone.