Osteologie 2019; 28(01): 66
DOI: 10.1055/s-0039-1680014
Forum Junge Wissenschaft der DGO
Georg Thieme Verlag KG Stuttgart · New York

Dickkopf-1 is dispensable for thyroid hormone-induced changes in bone remodeling

E Tsourdi
1   Universitätsklinik Dresden Carl Gustav Carus, Medizinische Klinik III, Endokrinologie, Diabetes und Metabolische Knochenerkrankungen, Dresden
,
J Colditz
1   Universitätsklinik Dresden Carl Gustav Carus, Medizinische Klinik III, Endokrinologie, Diabetes und Metabolische Knochenerkrankungen, Dresden
,
F Lademann
1   Universitätsklinik Dresden Carl Gustav Carus, Medizinische Klinik III, Endokrinologie, Diabetes und Metabolische Knochenerkrankungen, Dresden
,
E Rijntjes
2   Charité-Universitätsmedizin Berlin, Institut für Experimentelle Endokrinologie, Berlin
,
J Köhrle
2   Charité-Universitätsmedizin Berlin, Institut für Experimentelle Endokrinologie, Berlin
,
L Hofbauer
1   Universitätsklinik Dresden Carl Gustav Carus, Medizinische Klinik III, Endokrinologie, Diabetes und Metabolische Knochenerkrankungen, Dresden
,
M Rauner
1   Universitätsklinik Dresden Carl Gustav Carus, Medizinische Klinik III, Endokrinologie, Diabetes und Metabolische Knochenerkrankungen, Dresden
› Author Affiliations
Further Information
Elena Tsourdi
Universitätsklinik Dresden Carl Gustav Carus, Medizinische Klinik III, Endokrinologie, Diabetes und Metabolische Knochenerkrankungen, Fetscherstr. 74, 01307 Dresden, Deutschland

Publication History

Publication Date:
05 March 2019 (online)

 
 

    Introduction:

    Thyroid hormones are critical regulators of bone homeostasis, but their mechanisms of action remain incompletely understood. Exogenously induced hyper- and hypothyroidism in mice was recently found to be associated with an altered expression of the Wnt inhibitors sclerostin and Dickkopf-1 (Dkk1), key determinants of bone mass. In this study, we assessed the role of Dkk1 in thyroid-hormone induced changes in bone using conditional Dkk1 knockout mice.

    Methods:

    Male mice with a global (Dkk1fl/fl;Rosa26-CreERT2) or osteocyte-specific (Dkk1fl/fl;Dmp1:Cre) deletion of Dkk1 were pharmacologically rendered hypothyroid or hyperthyroid. The bone phenotype was analyzed using µCT analysis, dynamic histomorphometry, and serum concentrations of bone turnover markers.

    Results:

    Hyperthyroid mice with a global deletion of Dkk1 displayed a significant reduction of trabecular bone volume at the spine (-43%, p < 0.001) when compared to their euthyroid counterparts, while hypothyroid Cre-positive mice had a higher trabecular bone volume (+29%, p < 0.01). Similar changes were observed when Cre-negative hyperthyroid or hypothyroid mice were compared to their euthyroid littermates. Also, the osteocyte-specific deletion did not reverse the changes in bone mass induced by hypothyroidism and hyperthyroidism. Both, global and osteocyte-specific Dkk1 knockout mice displayed similar changes in bone turnover as their Cre-negative controls in the hyper- and hypothyroid state. While bone turnover was increased in hyperthyroidism, hypothyroidism potently suppressed bone turnover.

    Discussion:

    Dkk1 does not contribute to hypo- and hyperthyroid-induced changes in bone mass and bone turnover.


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    Elena Tsourdi
    Universitätsklinik Dresden Carl Gustav Carus, Medizinische Klinik III, Endokrinologie, Diabetes und Metabolische Knochenerkrankungen, Fetscherstr. 74, 01307 Dresden, Deutschland