Endocrine Abstracts

The hormonally active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) acting via the vitamin D receptor (VDR) is a potent transcriptional regulator, with effects on skeletal and extra-skeletal physiology. We have shown previously that skeletal responses to 1,25D also involve regulation of microRNAs (miRNAs); small non-coding RNAs with an emerging role in epigenetics. To assess the role of miRNAs in innate immune responses to 1,25D we utilised in v...

The hormonally active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) acting via the vitamin D receptor (VDR) is a potent transcriptional regulator, with effects on skeletal and extra-skeletal physiology. We have shown previously that skeletal responses to 1,25D also involve regulation of microRNAs (miRNAs); small non-coding RNAs with an emerging role in epigenetics. To assess the role of miRNAs in innate immune responses to 1,25D we utilised in v...

The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D), acting via the vitamin D receptor (VDR) is a potent regulator of gene expression, with effects on skeletal and extra-skeletal physiology. We have shown that actions of 1,25D on bone-forming osteoblasts also involve regulation of microRNAs (miRNAs) that play a key role in the functional development of these cells. In the current study, we have investigated miRNAs as mediators of innate and adaptive immune responses ...

Glucocorticoids (GCs) have potent immunomodulatory and anti-inflammatory effects and are widely used in the treatment of inflammatory diseases. Unfortunately, their long term administration causes serious systemic metabolic side effects including osteoporosis, muscle wasting and insulin resistance. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is responsible for the local conversion of inactive GCs to their active counterparts. It has been shown that many of the...

Local and systemic bone loss is a common complication in patients with chronic inflammatory disease. Previously, we have identified that glucocorticoid (GC) activation by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is increased within tissues such as bone during systemic inflammation. However, whilst effective at suppressing inflammation, in excess, GCs drive osteoporosis. To determine the contribution of 11β-HSD1 activated glucocorticoids to inf...

Glucocorticoids (GCs) have potent immunomodulatory and anti-inflammatory effects and are widely used in the treatment of inflammatory diseases. Unfortunately, their long term administration causes serious systemic metabolic side effects including osteoporosis, muscle wasting and insulin resistance. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is responsible for the local conversion of inactive GCs to their active counterparts. It has been shown that many of the...

Local and systemic bone loss is a common complication in patients with chronic inflammatory disease. Previously, we have identified that glucocorticoid (GC) activation by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is increased within tissues such as bone during systemic inflammation. However, whilst effective at suppressing inflammation, in excess, GCs drive osteoporosis. To determine the contribution of 11β-HSD1 activated glucocorticoids to inf...

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by progressive joint destruction and inflammatory activation and hyperproliferation of synoviocytes. We have previously reported a marked shift towards reduced local androgen metabolism in active RA, driven by changing expression of SRD5A1 and AKR1C3 within macrophages. In this study we examined the role of altered androgen metabolism and availability in the inflammatory function of both macr...

Muscle wasting is a common feature of inflammatory myopathies. Glucocorticoids (GCs), whilst effective at suppressing inflammation and inflammatory muscle loss, also cause myopathy with prolonged administration. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bidirectional GC activating enzyme, potently up-regulated by inflammation within mesenchymal derived tissues. We assessed the regulation of this enzyme with inflammation in muscle and examined its functi...

Both therapeutic glucocorticoids (GCs) and chronic inflammation are powerful inducers of systemic bone loss, resulting in osteoporosis and increased morbidity. Whilst GCs suppress inflammation, it is unclear how these factors interact to determine net bone metabolism. We investigated the balance between osteo-protective and osteo-destructive properties of GCs in the TNF-tg model of chronic inflammatory disease. Wild-type (WT) and TNF-tg mice were treated with corticosterone (1...