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    Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor

    Cell Metab. 2010 Jun 9;11(6):517-31.


    Using targeted deletion of the glucocorticoid receptor in osteoblast lineage- and osteoclast lineage cells, the authors found that glucocorticoid treatment of mice produced bone loss in wild type mice and mice without GR in osteoclast lineage cells. However, there was no effect of glucocorticoid treatment on bone mass in mice with targeted deletion of glucocorticoid receptors in osteoblast lineage cells.

    Authors: Rauch A, Seitz S, Baschant U, et. al

    Development of osteoporosis severely complicates long-term glucocorticoid (GC) therapy. Using a Cre-transgenic mouse line, we now demonstrate that GCs are unable to repress bone formation in the absence of glucocorticoid receptor (GR) expression in osteoblasts as they become refractory to hormone-induced apoptosis, inhibition of proliferation, and differentiation. In contrast, GC treatment still reduces bone formation in mice carrying a mutation that only disrupts GR dimerization, resulting in bone loss in vivo, enhanced apoptosis, and suppressed differentiation in vitro. The inhibitory GC effects on osteoblasts can be explained by a mechanism involving suppression of cytokines, such as interleukin 11, via interaction of the monomeric GR with AP-1, but not NF-kappaB. Thus, GCs inhibit cytokines independent of GR dimerization and thereby attenuate osteoblast differentiation, which accounts, in part, for bone loss during GC therapy.

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