Bone Abstracts

Glycosphingolipids (GSL) are essential structural components of mammalian cell membranes and lipid rafts that exert pleiotropic effects on cell survival, proliferation, and differentiation. Cancer associated GSL have been shown to promote tumor growth, angiogenesis, and metastasis; however their role in osteoclast (OC) activation and the development of osteolytic bone diseases such as multiple myeloma are not known. We investigated the hypothesis that GSL contribute to OC acti...

Glucocorticoid (GC)-induced osteoporosis (GIO) occurs in patients undergoing therapeutic intervention for inflammatory disorders such as rheumatoid arthritis and lupus. The effect of long-term GC administration on bone turnover was investigated in two frequently used mouse strains; C57BL/6 and CD1 in order to assess the influence of genetic background.GIO was induced in 12 weeks old female C57BL/6 and CD1 mice by s.c. insertion of long-term (60 days) rel...

Osteoclast resorption depends on their ability to reorganise their actin cytoskeleton and form the sealing zone. In order to resorb bone, osteoclasts become polarised by condensing their podosomes into a highly dynamic podosomal belt. The podosome turnover is regulated by several factors such as non-receptor tyrosine kinases, small GTPases and actin-binding proteins. The innate immune system responds to viral pathogens. Cytoplasmic double-stranded DNA activates the immune syst...

Fractures are very common and affect 2% of the population per annum. Fragility fractures represent the greatest unmet need and are associated with high rates of morbidity and mortality. Currently, there is no approved therapy for enhancing healing of fragility fractures. We previously reported that upregulation of the early inflammatory response following skeletal injury can promote fracture repair (Glass et al PNAS 2011). Inflammation represents the earliest response followin...

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Osteoporotic fractures are very common and represent an enormous unmet medical need. Our group has previously reported that addition of rTNF to the fracture site promotes fracture healing in C57/BL6 mice (Glass et al. PNAS 2011). Using a murine fracture model of endochondral healing, we observed that local addition of rTNF only accelerates fracture repair if administered within the first 24 h following injury. The optimal therapeutic dose is 1 ng. TNF is firs...