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

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

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