Environmental toxicants may modulate osteoblast differentiation by a mechanism involving the aryl hydrocarbon receptor.

Environmental toxicants may modulate osteoblast differentiation by a mechanism involving the aryl hydrocarbon receptor. Research Abstract Details 

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Environmental toxicants may modulate osteoblast differentiation by a mechanism involving the aryl hydrocarbon receptor. Abstract Text:

Elizabeth P Ryan,Jonathan D Holz,Mary Mulcahey,Tzong-Jen Sheu,Thomas A Gasiewicz,J Edward Puzas,Elizabeth P Ryan,Jonathan D Holz,Mary Mulcahey,Tzong-Jen Sheu,Thomas A Gasiewicz,J Edward Puzas,

The AHR mediates many of the toxicological effects of aromatic hydrocarbons. We show that AHR expression in osteoblasts parallels the induction of early bone-specific genes involved in maturation. The AHR may not only mediate the effects of toxicants, but with an as yet unidentified ligand, be involved in the differentiation pathways of osteoblasts. INTRODUCTION: Metabolic bone diseases arise as a result of an imbalance in bone cell activities. Recent evidence suggests that environmental toxicants may be contributing factors altering these activities. One candidate molecule implicated in mediating the toxic effects of exogenous compounds is the aryl hydrocarbon receptor (AHR). MATERIALS AND METHODS: Osteoblasts isolated from neonatal rat calvaria were analyzed for AHR expression by quantitative PCR, Western blot, and immunohistochemistry. In addition, AHR activation was evaluated by electromobility gel shift assay and fluorescence microscopy. RESULTS: Our findings showed AHR expression in mature osteoblasts in vivo. The pattern of AHR expression peaks after alkaline phosphatase and before induction of osteocalcin. We first show that AHR functions as a transactivating receptor in osteoblasts, as evidenced by its ligand-dependent migration to the nucleus and its association with known dioxin response elements. AHR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) mediated the induction of cytochrome p450 1A1 and cycloxygenase-2 protein levels. This effect could be inhibited by the potent AHR antagonist, 3'4 methoxynitroflavone. Furthermore, lead treatment of osteoblasts upregulates the expression of AHR mRNA and protein levels, supporting a novel mechanism whereby lead in the skeleton may increase the sensitivity of bone cells to toxicant exposure. CONCLUSIONS: These data imply that the AHR mediates the effects of aromatic toxicants on bone and that AHR expression is regulated during osteoblast differentiation.

Environmental toxicants may modulate osteoblast differentiation by a mechanism involving the aryl hydrocarbon receptor. Publishing Authors By Initials

EP Ryan,JD Holz,M Mulcahey,TJ Sheu,TA Gasiewicz,JE Puzas,EP Ryan,JD Holz,M Mulcahey,TJ Sheu,TA Gasiewicz,JE Puzas,

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Environmental toxicants may modulate osteoblast differentiation by a mechanism involving the aryl hydrocarbon receptor. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of bone and mineral research : the officia

VOLUME: 22

Page Numbers: 1571-80

Journal Abbreviation: J. Bone Miner. Res.

ISSN: 0884-0431

DAY: 2

MONTH: Oct

YEAR: 2007

Environmental toxicants may modulate osteoblast differentiation by a mechanism involving the aryl hydrocarbon receptor. Information

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LANGUAGE: eng

NlmUniqueID: 8610640

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Grant and Affiliation Information for Environmental toxicants may modulate osteoblast differentiation by a mechanism involving the aryl hydrocarbon receptor.

AFFILIATION: Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.

Country: United States

AGENCY: United States NIEHS

GRANT: T32 ES07026

ACRONYM: ES

MEDLINETA: J Bone Miner Res

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