Bone Abstracts

Hyperthyroidism in mice is associated with a low bone mass, an increased bone turnover and high serum levels of sclerostin, a potent Wnt inhibitor. Here, we explored the effects of either reducing bone turnover with bisphosphonates or increasing bone formation with neutralizing sclerostin antibodies (Scl-Ab) on bone mass and estimated strength in hyperthyroid mice.Twelve-week-old C57BL/6 male mice were rendered hyperthyroid by adding L-thy...

Introduction: Gaucher disease (GD), the most prevalent glycolipid storage disease, is an autosomal recessive metabolic disorder that is caused by an inherited deficiency of the lysosomal enzyme, glycocerebrosidase. This defect leads to reduce enzyme activity, resulting in the accumulation of glucosylceramide in cells of the monocyte-macrophages linage, known as Gaucher cells. Common presenting features include anemia, thrombocytopenia, hepatosplenomegaly and bone abnormalities...

Glucocorticoids (GC) are effective drugs in the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited by negative effects on bone mass and strength, resulting in increased osteoporotic fractures. Conditional knockout mice demonstrated that the GR in osteoblasts is essential for GC-dependent bone loss. Recent studies show that GC profoundly inhibit Wnt signaling by stimulating the expression of Wnt antagonists such as dickkopf-1...

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Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein that controls the engulfment of apoptotic cells and exerts anti-inflammatory effects. It has been implicated in the pathogenesis of several diseases, but its role in the bone microenvironment is still unknown. Here we tested the hypothesis that MFG-E8 also regulates bone metabolism and the development of arthritis.MFG-E8 expression was detected in mouse bones and primary murine osteobl...

Introduction: Bone metastases represent a frequent complication of breast cancer and are characterized by increased tumour-driven activation of osteoclasts and subsequent bone loss. Aminobisphosphonates inhibit osteoclast function and are established therapies of skeletal metastases. Similar to statins, they block the mevalonate pathway and are thought to have direct anti-tumour effects. Here, we report on the anti-tumour potential of a sequential inhibition of the mevalonate ...

Introduction: Collagen and glycosaminoglycans (GAGs) such as hyaluronan (HA) and chondroitin sulfate (CS) are basic elements of bone structure and collagen-GAG composites are currently developed for a wide range of applications. Here, we report on the molecular and cellular effects of GAGs and their sulfated derivatives on osteocytes, which are fundamental orchestrators of bone remodeling.Materials and methods: The effects of native and sulfate-modified ...

The osteoclast-associated receptor (OSCAR), primarily described as a co-stimulatory regulator of osteoclast differentiation, represents a novel link between bone metabolism and vascular biology. Previously, we identified OSCAR on endothelial cells responding to the proatherogenic factor oxidized low density lipoprotein (oxLDL). Additionally, OSCAR expression was increased in the aorta of atherogenic apoE-knock-out (apoE-KO) mice, where it was further induced by feeding a high-...

Owing to their anti-inflammatory effects, steroid therapy using glucocorticoids (GCs) is still part of the treatment of rheumatoid arthritis (RA), despite several severe side effects like glucocorticoid-induced osteoporosis (GIO). Until now the molecular mechanisms underlying the beneficial and side effects of GC therapy are poorly understood. GCs exert their actions via the glucocorticoid receptor (GR) that alters gene expression by either binding as a dimer to GC response el...

Background: The tyrosine kinase inhibitor (TKI) imatinib is applied as front-line treatment in adult and pediatric patients with chronic myeloid leukemia (CML) in order to selectively inhibit the causative oncogenic BCR-ABL1 tyrosine kinase. However, TKIs exhibit off-target effects on further kinases involved in the regulation of bone metabolism. As consequence, pediatric patients display longitudinal growth retardation while on imatinib treatment. As CML is a rare disease in ...