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...

Chronic kidney disease (CKD) is defined according to the presence of kidney damage and level of kidney function – irrespective of the type of kidney disease (diagnosis). Among individuals with chronic kidney disease, the stages are defined based on the level of glomerular filtration rate. From infancy through young adulthood, the major causes of CKD arise from congenital abnormalities of the kidneys and urinary tract (CAKUT), acquired or congenital forms of nephrotic synd...

Introduction: The calcium sensing receptor presence (CaSR) at the surface of the osteocytes has never been clearly investigated. The CaSR are known to be express on osteoblasts. Osteocytes being old osteoblasts embedded in the matrix, this expression of CaSR is likely, and could constitute a key role to calcium signalling.Strontium ranelate (SrRan) has shown to activate osteoblasts by fixation on CaSR (Chattopadhyay N 2007, Biochem Pharmacol; Hu...

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...

In advanced ER+ve breast cancer, the propensity of bone involvement is 85%. Similarly in advanced lung cancer, 30–40% of patients develop bone metastases, and as recent advances in lung cancer therapies improve survival, the number of patients living with bone metastases is expected to increase. At the same time there is a paucity of especially ER+ and osteoblastic animal models available. We present herein the development of four mouse models of breast and lung cancer su...

Introduction: Recessive osteogenesis imperfecta (OI) is caused by mutations in genes encoding proteins involved in post-translational interactions with type I collagen. Types VII–IX OI involve defects in the collagen prolyl 3-hydroxylation complex, which modifies α1(I)Pro986. PPIB encodes CyPB, a complex component with PPIase activity and the major isomerase facilitating collagen folding. We investigated the role of CyPB in collagen post-translational modifications a...

Reduced availability of oxygen, i.e. hypoxia, could occur during disuse, bone development, and fracture. Cartilage tissue is avascular in nature and the microenvironment of cartilage is hypoxic. Hypoxic regulation of gene expression generally involves activation of the hypoxia-inducible factor (HIF) transcription pathway. Receptor activator of nuclear factor-kappaB ligand (RANKL) is an osteoblast/stromal cell derived essential factor for osteoclastogenesis. Hypoxia-induced enh...

Introduction: Umbilical cord blood (UCB) is increasingly used in hematopoietic stem cell (HSC) transplantations; however, the low cell numbers are still remaining as a limiting factor for proper engraftment. Osteoblasts are major constituents of HSC niche and play important roles in regulating HSC self-renewal and differentiation. Recently, extracellular vesicles (EVs) have been implicated in stem cell fate regulation via horizontal transfer of proteins and nucleic acids betwe...

Background: Cancer patients often receive a combination of drugs that target both the microenvironment and the tumour cells. However, the role of the bone microenvironment (BME) in mediating peripheral breast cancer growth remains poorly understood. This is the first study to determine whether reduced subcutaneous tumour growth following combination therapy is due to direct interactions between the drugs and tumour cells or through zoledronic acid induced alterations to the BM...

RANKL, the receptor activator of nuclear factor kappa B ligand, is an essential factor for the formation of mature osteoclasts. Together with its receptor RANK and its antagonist Osteoprotegerin (OPG) RANKL is a key regulator in bone metabolism1. RANKL is a membrane-bound protein that can be segregated to a soluble form (sRANKL), whereas only the latter has been reported to be bioactive2. Due to its low circulating levels and the nature of the analyte bin...