Bone Abstracts

Bone is the primary site of metastasis for breast cancer, which leads mainly to osteolytic lesions, Cancer cells can expand into the bone for their ability to ‘dialogue’ with resident cells, interfering with the physiological processes of bone turnover. In this study, a large-scale analysis comparing gene expression of biopsies of bone and visceral metastases from human breast cancer patients showed that the receptor (G protein-coupled) activity modifying protein-2 (...

Autosomal dominant osteopetrosis type 2 (ADO2) is a rare genetic disease due to reduced osteoclast function. Clinical manifestations are variable, and in some cases the symptoms, including frequent fractures, osteomyelitis, hematologic and neural failures, are already evident during childhood and worsen with age. In 70% of cases, ADO2 is caused by heterozygous dominant negative mutations of the CLCN7 gene, encoding the Cl−/H+ antiporter type 7. We hypothesized that silen...

Cysteine-rich with EGF like domains 2 (Creld2) has recently been identified as an endoplasmic reticulum (ER) stress inducible gene in the context of skeletal dysplasia caused by mutant protein accumulating in the ER eliciting an unfolded protein response (UPR). Creld2 was originally implicated in ER stress following the treatment of Neuro2α cells with thapsigargin. Furthermore, the promoter of Creld2 contains an ER stress activating transcription factor ...

Objectives: ADO2 is a genetic bone disease induced by dominant negative mutations of the proton/chloride antiporter ClC7 encoded by the CLCN7 gene. In osteoclasts, ClC7 is crucial for lysosome function and resorption lacuna acidification. However, Clcn7 is expressed in several cell types in various organs, including brain, lungs, kidneys and spleen. Therefore, we asked whether Clcn7 mutations could affect other tissues beyond the bone.<p class="a...

Breast cancer (BrCa) patients with metastases restricted to bone (BO) show a longer overall survival compared to BrCa patients developing bone and visceral metastases (BV). To unveil the molecular mechanisms that segregate these two BrCa patient groups, we performed microarray analyses on bone metastasis samples from BO and BV patients, finding in the latter a set of up-regulated genes involved in oxygen metabolism. We focused on Hemoglobin B (HBB) and evaluated its expression...

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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...

ADO2 is a debilitating genetic bone disease causing multiple fractures and other severe symptoms. A mouse model of ADO2, harbouring the heterozygous Clcn7G213R gene mutation, phenocopies the human syndrome. The Clc7 gene encodes the ClC7 dimeric 2Cl−/1H+ antiporter that is almost ubiquitously expressed, although the mutations hit especially the osteoclasts impairing bone resorption. By immunofluorescence, we observed that the mutant ClC7 ...

We previously demonstrated the involvement of Lcn2 in bone loss induced by mechanical unloading. This prompted us to investigate bone phenotype of Lcn2−/− mice by μCT, which showed an osteopenic phenotype, characterized by 40% lower trabecular bone volume, 50 and 21% lesser trabecular number and thickness, respectively, and 20% higher trabecular separation, compared to WT, while cortical thickness was significantly lower (40%) only in elderly Lcn2<s...

Angiogenesis and osteogenesis are tightly linked and dependent on each other. Lipocalin 2 (LCN2) is a mechanoresponding adipokine, strongly upregulated in osteogenic cells subjected to microgravity (0.08–0.008 g), in which it impairs osteogenesis and upregulates the osteoclastogenic cytokine, RANKL. We investigated the role of LCN2 in the crosstalk between angiogenesis and osteogenesis in simulated microgravity conditions as a model of mechanical unloading. Mouse and huma...