Roles for B[a]P and FICZ in subchondral bone metabolism and experimental temporomandibular joint osteoarthritis via the AhR/Cyp1a1 signaling axis

Abstract Bone loss due to smoking represents a major risk factor for fractures and bone osteoporosis. Signaling through the aryl hydrocarbon receptor (AhR) its ligands contributes both homeostasis inflammatory diseases. It remains unclear whether same AhR signaling axis affects temporomandibular joint (TMJ). The aim of this study was investigate possible mechanisms which mediate in TMJ smoking. In particular, benzo[ ]pyrene (B[ ]P), carcinogen tobacco smoke, induces expression target gene, Cyp1a1, mandibular condyles. Possible functions an endogenous ligand FICZ, were also investigated TMJ-osteoarthritis (OA) mouse model. B[ ]P administered orally wild-type −/− mice metabolism subsequently examined. TMJ-OA induced with forceful opening mouth. Therapeutic FICZ detected μCT histology. Exposure accelerated subchondral bone. This manifested osteoclastic resorption upregulated Cyp1a1 -dependent manner. model TMJ-OA, exhibited dose-dependent rescue by repressing osteoclast activity. Meanwhile, vitro, pre-treatment reduced RANKL-mediated osteoclastogenesis. regulates via Cyp1a1. ligand, can prevent regulating differentiation.