Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2013) 32 S8.1 | DOI: 10.1530/endoabs.32.S8.1

ECE2013 Symposia Action of glucocorticoids on bone (3 abstracts)

Glucocorticoid action on the skeleton

Jan Tuckermann


Institute for General Zoology and Endocrinology, University of Ulm, Ulm, Germany.


Glucorticoids (GCs) belong since their discovery to the standard therapy of rheumatoid arthritis (RA), a severe auto-inflammatory bone disease. One major side effect of GCs affects the skeleton itself leading to GC induced osteoporosis (GIO), the most secondary osteoporosis.

To optimize anti-inflammatory therapies utilizing steroids a profound understanding of GC action on the interface of inflammation and skeletal integrity is required.

GCs act via a receptor (GR) that can alter gene expression by binding as a dimer to GC responsible elements in the promoter region of target genes or by interacting with and thus interfering with other transcription factors as a monomer. We determined the contribution of molecular mechanisms and cell types critically involved in anti-inflammatory effects of GCs in RA and on skeleton using conditional and function selective GR knockout mice.

We made the surprising observation that for suppression of inflammation in several arthritis models GR dimerization is absolutely required in part including a specific action in T cells.

In contrast for GC induced bone loss we demonstrated in a model of GIO that unexpectedly interaction of the GR monomer with AP-1, but not NF-kB in osteoblasts is decisive for bone loss.

Our findings define new criteria for SEGRM that act anti-inflammatory and protect the bone. Indeed we identified one lead-compound that still suppresses NF-kB dependent gene expression but does not affect osteoblast differentiation and activity.

Furthermore we identified novel GR target genes by functional genomics and developed a screening platform for novel GR agonist-derivatives not affecting osteoblast function.

Taken together, our approach gives new insights into GC action on arthritis and bone that can be translated into new concepts for anti-inflammatory therapies preventing GIO.

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