Searchable abstracts of presentations at key conferences on calcified tissues

ba0001pp147 | Cancer and bone: basic, translational and clinical | ECTS2013

Involvement of the co-receptor RAMP2 in the progression of breast cancer-induced osteolytic lesions

Cappariello Alfredo , Rucci Nadia , Capulli Mattia , Muraca Maurizio , Teti Anna

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 (...

ba0004oc14 | (1) | ICCBH2015

Small interfering RNAs as an innovative therapeutic approach for the autosomal dominant osteopetrosis type 2 (ADO2)

Capulli Mattia , Maurizi Antonio , Ventura Luca , Rucci Nadia , Teti Anna

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...

ba0005lb12 | (1) | ECTS2016

The role of Creld2 in skeletal development and homeostasis

Dennis Ella , Capulli Mattia , Teti Anna , Pirog Katarzyna , Briggs Michael

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 ...

ba0006p189 | (1) | ICCBH2017

A deep phenotyping of autosomal dominant osteopetrosis type 2 (ADO2) mouse model revealed multiorgan dysfunctions

Maurizi Antonio , Capulli Mattia , Patel Rajvi , Rucci Nadia , Teti Anna

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...

ba0003oc5.3 | Important pathways in bone biology and cancer | ECTS2014

Beta haemoglobin (hbb) is a novel marker of breast cancer progression

Capulli Mattia , Angelucci Adriano , Teti Anna , Sanita Patrizia , Ventura Luca , Rucci Nadia

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...

ba0003pp405 | Other diseases of bone and mineral metabolism | ECTS2014

Innovative cell-based strategy for systemic delivery of soluble RANKL in RANKL-deficient osteopetrotic mice

Cappariello Alfredo , Paone Riccardo , Capulli Mattia , Rucci Nadia , Muraca Maurizio , Teti Anna

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...

ba0005ht1 | (1) | ECTS2016

Storage disease and neurological phenotype in autosomal dominant osteopetrosis type 2 (ADO2). A preclinical study

Maurizi Antonio , Capulli Mattia , Cortes Juliana , Rito Laura Di , Rucci Nadia , Teti Anna

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 ...

ba0005oc4.3 | Catabolism and metabolism | ECTS2016

Connecting the dots between bone and energy metabolism: the role of Lipocalin 2

Capulli Mattia , Gemini-Piperni Sara , Maurizi Antonio , Ponzetti Marco , Teti Anna , Rucci Nadia

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...

ba0005oc6.3 | Development and differentiation (or Aging) | ECTS2016

The critical biomechanical role of Lipocalin 2 in the crosstalk between endothelium and osteoblasts in unloading conditions.

Veeriah Vimal , Capulli Mattia , Zanniti Angelo , Chatterjee Suvro , Rucci Nadia , Teti Anna

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...