Deletion of the glucocorticoid receptor in osteoblasts and osteocytes drives trabecular bone loss in Col2.3-Cre and OG2-Cre knockout mice.
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Overview
abstract
Studies using the 11β-HSD2 transgenic mouse model have established that endogenous glucocorticoids in bone forming cells are important for normal trabecular and cortical bone mass and structure. However, the role of the glucocorticoid receptor in mature osteoblasts and osteocytes for maintaining the skeleton remains unknown. We generated two glucocorticoid receptor knockout models targeting mature osteoblasts and osteocytes (by utilizing the Col2.3-Cre or OG2-Cre). We found that deletion of the glucocorticoid receptor using either knockout model profoundly reduced vertebral bone volume fraction across various ages from 7 to 26 weeks in male and female mice compared to wild-type animals. At the tibia we found sex-specific differences in trabecular bone volume fraction, which was reduced in male but not female Col2.3-Cre and OG2-Cre glucocorticoid receptor knockout mice. Compared to trabecular bone, changes in cortical bone mass and structure in glucocorticoid receptor knockout mice were age and model dependent. Young male and female Col2.3-Cre glucocorticoid receptor knockout mice exhibited a reduction in cortical area and thickness. However, in male but not female OG2-Cre glucocorticoid receptor knockout mice, cortical area fraction and cortical thickness were increased compared to control animals. By 26 weeks of age, cortical bone structure was comparable in Col2.3-Cre and OG2-Cre glucocorticoid receptor knockout mice compared to wild-type animals. Our results provide evidence that glucocorticoid receptor signalling in mature osteoblasts and osteocytes is critical for the maintenance of trabecular and cortical bone mass and structure.
