The rise in expression and activity of 11β-HSD1 in human mesenchymal progenitor cells induces adipogenesis through increased local cortisol synthesis.

11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) plays an important role in pre-receptor glucocorticoid metabolism. This enzyme is expressed in bone, increases with age, and catalyzes the conversion of the inactive glucocorticoid cortisone into the active glucocorticoid cortisol and vice versa. Here we hypothesized that the physiological activity of 11β-HSD1 to produce cortisol in human mesenchymal progenitor cells (hMSC) is principally sufficient to shift the differentiation potential in the direction of adipogenic.

Crohn's disease patient serum changes protein expression in a human mesenchymal stem cell model in a linear relationship to patients' disease stage and to bone mineral density.

Background: Crohn's disease (CD) is associated with a higher prevalence of osteoporosis, a complication that is recognized as a significant cause of morbidity. Its pathogenesis is controversial, but the activity of CD is one contributing factor.

Methods: We stimulated SCP-1 cells (mesenchymal stem cell line) under osteogenic conditions with serum from adult patients with CD in the symptomatic phase (SP) and in remission (R) and with control sera.

IL-6, IL-1β, and TNF-α only in combination influence the osteoporotic phenotype in Crohn's patients via bone formation and bone resorption.

Background: Crohn´s disease (CD) is associated with a higher prevalence of osteoporosis. The pathogenesis of bone affliction remains controversial, especially if inflammatory cytokines or glucocorticoid therapy are the main contributors. In postmenopausal osteoporosis, bone resorption is induced by IL-6, IL-1β and TNF-α.

Genetic polymorphisms in 11β-hydroxysteroid dehydrogenase type 1 correlate with the postdexamethasone cortisol levels and bone mineral density in patients evaluated for osteoporosis.

Context: Higher physiological cortisol levels may increase the risk of age-related osteoporosis. We hypothesized that common polymorphisms in the cortisol synthesis enzyme 11β-hydroxysteroid dehydrogenase (HSD11B) may cause interindividual variations in cortisol levels and age-related bone loss.

Study Design And Patients: We performed a retrospective study in a cohort of 452 ambulatory patients under evaluation for osteoporosis.