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Hochrath, K.* ; Ehnert, S.* ; Ackert-Bicknell, C.L.* ; Lau, Y.* ; Schmid, A.* ; Krawczyk, M.* ; Hengstler, J.G.* ; Dunn, J.* ; Hiththetiya, K.* ; Rathkolb, B. ; Micklich, K.* ; Hans, W. ; Fuchs, H. ; Gailus-Durner, V. ; Wolf, E.* ; Hrabě de Angelis, M. ; Dolley, S.* ; Paigen, B.* ; Wildemann, B.* ; Lammert, F.* ; Nüssler, A.K.*

Modeling hepatic osteodystrophy in Abcb4 deficient mice.

Bone 55, 501-511 (2013)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 did not 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Chronic colangitis; Liver fibrosis; Osteoporosis; RANK ligand; Vitamin D; Chronic Liver-disease ; Growth-factor-beta ; Sclerosing Cholangitis ; Cortical Bone ; Mdr2 ; Osteoporosis ; Fibrosis ; Bile ; Transplantation ; Osteopontin
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 2013
ISSN (print) / ISBN 8756-3282
e-ISSN 1873-2763
Zeitschrift Bone: Official Journal of the International Bone and Mineral Society
Quellenangaben Band: 55, Heft: 2, Seiten: 501-511 Artikelnummer: , Supplement: ,
Verlag Elsevier
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
POF Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500600-003
G-500600-001
G-501900-063
PubMed ID 23545228
DOI 10.1016/j.bone.2013.03.012
WOS ID WOS:000320896600033
Scopus ID 84878897600
Erfassungsdatum 2013-06-06
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