Bone Abstracts

Introduction: Age-related bone diseases, such as osteoarthritis (OA) and osteoporosis (OP), are strongly associated with sarcopenia and muscle fiber atrophy. Potential mechanisms involved in the reduction of skeletal muscle mass during sarcopenia converge on the failure of satellite cells in replacing and repairing damaged muscle fibers. Myostatin and bone morphogenetic proteins (BMPs) are molecules able to regulate muscle mass homeostasis by activating satellite stem cells [4...

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In autosomal recessive osteopetrosis due to mutations of the TNFSF11 gene, deficiency of the pro-osteoclastogenic cytokine RANKL prevents osteoclast formation. RANKL is a membrane-bound protein cleaved into active soluble (s)RANKL by various enzymes, including metalloproteinase 14 (MMP14). We created a bio-device that released sRANKL and induced osteoclastogenesis in tnfsf11−/− mice. We tested various RANKL cell sources, and used mouse primary calvarial osteoblasts...

Bone disease is the most frequent complication in multiple myeloma (MM) resulting in pain, bone fractures, spinal cord compression and hypercalcemia. Within the bone marrow microenvironment (BMM), MM cells interact with bone cells to enhance bone resorption activity and compromise new bone formation mechanism; in turn, BMM provides a survival and drug resistance framework by interaction of MM cells with bone marrow components. Exosomes are important mediators of crosstalk betw...

LIGHT is a TNF superfamily member, expressed by activated T cells. It is involved in erosive bone disease, such as rheumatoid arthritis where it stimulates osteoclastogenesis. In multiple myeloma, LIGHT promotes osteolysis by increasing osteoclastogenesis and inhibiting osteoblastogenesis. We investigated whether LIGHT has a role in the osteolytic bone metastatic process induced by non small cell lung cancer (NSCLC), which is a tumor with a marked osteotropism. We analysed by ...

Introduction: Normal mechanical loading potently induces bone formation via effects on osteocytes. Current investigations of mechanical loading of bone do not reflect the interactions of the cells within it, mostly focusing on mechanical loading of osteoblasts in monolayers. Existing 3D models do not elucidate the osteoblast-osteocyte interactions that regulate mechanically-induced bone formation. We developed a novel in vitro 3D co-culture model of bone1 t...

Despite mutations in SQSTM1 gene have been detected in up to 50% of patients with familial Paget’s disease of bone (PDB), their prevalence is low in sporadic PDB, likely due to the presence of additional predisposition genes. Recently, at least seven genes were associated with PDB in genome-wide-association studies, including polymorphic variation in OPTN,encoding for optineurin. In particular, a single OPTN variant (rs1561570) was highly associated with...

We previously evidenced a reduced response to i.v. pamidronate in Q15STM1 mutation carriers (Q15STM1+) with Paget’s disease of bone (PDB). In order to confirm and extend this observation, we investigated the effect of Q15STM1 mutation and polymorphisms in three genes associated with PDB (TNFRSF11A; OPTN; TNFRSF11B) on the response to bisphosphonates. First, a retrospective study was performed in 335 patients treated wi...

Context: Anorexia nervosa (AN) occurs predominantly in females, most frequently during adolescence and it is generally associated with amenorrhoea. AN increases the risk for impaired bone health and for low bone mineral density (BMD) by a mechanism which has not been yet well defined.Objective: The study purpose was to further characterize bone metabolism in AN with amenorrhoea, and so with oestrogen deficiencyDesign: AN patients w...

Bone is constantly being molded and shaped by the action of osteoclasts and osteoblasts. A proper equilibrium between both cell types metabolic activities is required to ensure an adequate skeletal tissue structure, and it involves resorption of old bone and formation of new bone tissue. It is reported that treatment with antiepileptic drugs (AEDs) can elicit alterations in skeletal structure, in particular in bone mineral density. Nevertheless, the knowledge regarding the eff...