Aryl hydrocarbon-mediated inhibition of osteogenesis, reversal by resveratrol, a novel aryl hydrocarbon receptor antagonist

grantor: University of TorontoAryl hydrocarbon receptor ligands (AhR ligands) are environmental contaminants found in cigarette smoke and other sources of air pollution. The prototype is TCDD (2,3,7,8 tetrachlorodibenzo-p-dioxin). There is increasing evidence linking cigarette smoking to osteoporosis and periodontal disease, but the mechanism is not well understood. By using resveratrol (3,5,4' -trihydroxystilbene), a plant antifungal compound that we recently demonstrated to be a pure AhR antagonist, we investigated the effects of TCDD on osteogenesis, hypothesizing that TCDD would inhibit bone formation in bone forming cultures and that this inhibition would be antagonized by resveratrol. We used the chicken periosteal osteogenesis (CPO) model which forms bone in vitro in a pattern morphologically and biochemically similar to that seen in vivo. The effects of drugs on various stages of bone formation such as differentiation, matrix production and mineralization can be assessed. Thus, this system is useful for studying osteogenesis through the measurement of alkaline phosphatase (ALP) activity (bone call differentiation, and phosphate or calcium accumulation (mineralization). To confirm our findings, we also used a mammalian (rat) cell line that produces bone in vitro. (Abstract shortened by UMI.)M.Sc