|IQBAL, JAMEEL - University Of Pennsylvania|
|SUN, LI - University Of Pennsylvania|
|YUEN, TONY - Mount Sinai School Of Medicine|
|BAB, ITAI - Hebrew University|
|LEU, NICOLAE - University Of Pennsylvania|
|WAGAGE, SAGIE - University Of Pennsylvania|
|HUNTER, CHRISTOPHER - University Of Pennsylvania|
|NEBERT, DANIEL - University Of Cincinnati|
|ZAIDI, MONE - Mount Sinai School Of Medicine|
Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/21/2013
Publication Date: 7/2/2013
Publication URL: http://handle.nal.usda.gov/10113/58061
Citation: Iqbal, J., Sun, L., Cao, J.J., Yuen, T., Bab, I., Leu, N., Wagage, S., Hunter, C., Nebert, D.W., Zaidi, M. 2013. Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of CYP1 enzymes. Proceedings of the National Academy of Sciences. 110(27):1115-11120.
Interpretive Summary: Smoking is one of the risk factors for osteoporosis and fracture. Cigarettes contain at least 150 known toxic molecules, such as benzo[a]pyrene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and 3-methyl cholanthrene. Here, we present genetic and pharmacological evidence that these smoke toxins stimulate osteoclastogenesis, suggesting smoke carcinogens promote bone resorption.
Technical Abstract: Smoking is a major risk factor for osteoporosis and fracture. Here, we show that smoke toxins and environmental chemicals such as benzo[a]pyrene (BaP), 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD), and 3-methyl cholanthrene, which are well known aryl hydrocarbon receptor (AHR) agonists, induce osteoclast formation, although the precise mechanisms remain constroversial. We therefore investigated the ex vivo as well as in vivo effects of BaP and TCDD on primary bone marrow cells and mouse models of AHR and AHR regulated CYP1 (CYP1A1, CYP1A2 and CYP1B1) knockout mice.