Aryl hydrocarbon receptor-mediated impairment of chondrogenesis and fracture healing by cigarette smoke and benzo(α)pyrene

摘要: The clinical literature strongly suggests that bone healing in cigarette smokers is impaired. Since smoke (CS) contains numerous polycyclic aromatic hydrocarbons (PAHs), and since dioxins impair formation vivo via the Aryl Hydrocarbon Receptor (AHR), we investigated impact of PAH/AHR signaling on chondrogenesis a mouse tibial fracture model. We established CS activates AHR fractures by up-regulating target gene cytochrome p4501A1 (Cyp1A1). For vitro studies, employed limb bud micromass After confirming chondrocytes express during differentiation, treated cells with prototypical PAH found CS, benzo(α)pyrene (BaP), or extract (CSE). Both BaP CSE inhibited mesenchymal generated from E11 buds, also accelerating chondrocyte hypertrophy cultures E12 buds. Detection DNA adducts BaP-treated distinct phenotypic effects may be due to reactive metabolites. Blockade antagonist MNF reverses BaP, but not CSE, suggesting inhibition AHR-independent. Correlating these results, calluses mice were smaller contained less mineralized tissue than vehicle controls. Overall, identified as potent inhibitor correlated similar those itself, basis for PAHs key compounds influence repair. J. Cell. Physiol. 227: 1062–1070, 2012. © 2011 Wiley Periodicals, Inc.