期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 273, 期 1, 页码 219-226出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2013.09.002
关键词
Aryl hydrocarbon receptor; Bone microstructure; Micro-computed tomography; Bone strength; Tissue quality; Nanoindentation
资金
- European Commission [QLK4-CT-2002-02528]
- Yrjo Jahnsson Foundation
- National Doctoral Programme of Musculoskeletal Disorders and Biomaterials (TBDP)
Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr(-/-)) and wild-type (Ahr(+/+)) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 mu g/kg bw. Bones were examined with micro-computed tomography, nano-indentation and biomechanical testing. Serum levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr(+/+) mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr(-/-) mice displayed a slightly modified bone phenotype as compared with untreated Ahr(+/+) mice, while TCDD exposure caused only a few changes in bones of Ahr(-/-) mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr(+/+) mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. (C) 2013 Elsevier Inc. All rights reserved.
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