Modeling hepatic osteodystrophy in Abcb4 deficient mice.
Document Type
Article
Publication Date
8-2013
JAX Source
Bone 2013 Aug; 55(2):501-11
ISSN
1873-2763
PMID
23545228
Abstract
Hepatic osteodystrophy (HOD) denotes the alterations in bone morphology and metabolism frequently observed in patients with chronic liver diseases, in particular in case of cholestatic conditions. The molecular mechanisms underlying HOD are only partially understood. In the present study, we characterized the bone phenotypes of the ATP-binding cassette transporter B4 knockout mouse (Abcb4(-/-)), a well-established mouse model of chronic cholestatic liver disease, with the aim of identifying and characterizing a mouse model for HOD. Furthermore, we investigated the influence of vitamin D on bone quality in this model. The bone morphology analyses revealed reduced bone mineral contents as well as changes in trabecular bone architecture and decreased cortical bone densities in Abcb4(-/-) mice with severe liver fibrosis. We observed dysregulation of genes involved in bone remodeling (osteoprotegerin, osteocalcin, osteopontin) and vitamin D metabolism (7-dehydrocholesterol reductase, Gc-globulin, Cyp2r1, Cyp27a1) as well as alterations in calcium and vitamin D homeostasis. In addition, serum RANKL and TGF-β levels were increased in Abcb4(-/-) mice. Vitamin D dietary intervention was only partially able to restore the bone phenotypes of Abcb4(-/-) animals. We conclude that the Abcb4(-/-) mouse provides an experimental framework and a preclinical model to gain further insights into the molecular pathobiology of HOD and to study the systemic effects of therapeutic interventions. Bone 2013 Aug; 55(2):501-11
Recommended Citation
Hochrath K,
Ehnert S,
Ackert-Bicknell CL,
Lau Y,
Schmid A,
Krawczyk M,
Hengstler J,
Dunn J,
Hiththetiya K,
Rathkolb B,
Micklich K,
Hans W,
Fuchs H,
Gailus-Durner V,
Wolf E,
de Angelis M,
Dooley S,
Paigen B,
Wildemann B,
Lammert F,
Nüssler A.
Modeling hepatic osteodystrophy in Abcb4 deficient mice. Bone 2013 Aug; 55(2):501-11