Endocrine Abstracts

Therapeutic glucocorticoids are used in rheumatoid arthritis (RA) to reduce inflammation and bone destruction. We recently reported that primary synovial fibroblasts generate active glucocorticoids via expression of 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1). This enzyme activates cortisol from inactive cortisone (and prednisolone from prednisone) and this activity is up-regulated by inflammation. We have now examined glucocorticoid metabolism in synovial tissu...

Synovial fibroblasts (SFs) form a substantial component of inflamed rheumatoid synovium and generate endogenous glucocorticoids (GCs) during inflammation. Recently, production of DKK-1 (a Wnt signalling inhibitor that reduces bone formation) by SFs in response to TNFα has been proposed to be the master regulator of inflammatory osteoporosis. We have identified that in addition to TNFα, GCs potently induce DKK-1 secretion. This may provide a novel mechanism whereby lo...

High dose glucocorticoids are effective in suppressing inflammatory synovitis but have adverse effects on other connective tissues. In inflammatory arthritis glucocorticoids suppress the capacity of synovial fibroblasts (SFs) to recruit leukocytes to the joint whereas poor skin healing is due to impaired dermal fibroblast (DF) function. It is unknown whether these clinical differences are due to similar or distinct effects of glucocorticoids on fibroblast function.<p class...