Bone Abstracts

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...

Background: Cabozantinib (CBZ) is a receptor tyrosine kinase inhibitor with activity against MET, VEGFR2, FLT3, c-KIT, and RET. Pre-clinical studies in models of prostate cancer bone metastasis demonstrated that CBZ treatment induced both a suppression of tumour growth and an alteration in bone remodelling, suggesting that both tumour and bone microenvironment represented potential CBZ targets. This is the first study exploring the potential direct activity of CBZ in bone usin...

Activins belong to the transforming growth factor-β superfamily, and they regulate bone formation by controlling both osteoclast and osteoblast behaviour. We have previously shown that activin-A strongly inhibited matrix mineralization in osteoblast cultures, and that activin A-signalling was most effective before the onset of mineralization.The aim of this study was therefore to investigate how an early activin-A pulse affected osteoblast mineraliz...

Dominant osteogenesis imperfecta (OI) is a bone disease mainly caused by collagen type I mutations and characterized by bone fragility and growth delay. Nowadays no definitive cure is available. A zebrafish OI model (Chihuahua) carrying an heterozygous G574D substitution in the α1 chain of collagen type I was generated by ENU mutagenesis and is available in our laboratory. Control (WT) and mutant (Chi+/−) fish growth was followed up from day 1 post fertilization to ...

Osteogenesis imperfecta is a clinically heterogeneous heritable connective tissue disorder. Most OI cases are due to mutations in type I collagen genes, COL1A1 and COL1A2 encoding the pro-alpha1(I) and pro-alpha2(I) chains respectively. However, genotype-phenotype correlation has not been completely elucidated yet. In this study we evaluated a familial case including a mother and a daughter, classified as OI type I. The daughter had more severe clinical featu...

Osteogenesis imperfecta is a clinically heterogeneous heritable connective tissue disorder. Most OI cases are due to mutations in type I collagen genes, COL1A1 and COL1A2 encoding the pro-alpha1(I) and pro-alpha2(I) chains respectively. However, genotype–phenotype correlation has not been completely elucidated yet. In this study we evaluated a familial case including a mother and a daughter, classified as OI type I. The daughter had more severe clinical ...

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 ...

Background and Objectives: Rheumatoid arthritis (RA) is a chronic disease characterized by severe bone destruction which has been associated with altered lipid metabolism. Apolipoprotein E (Apo E) is a lipoprotein mainly produced by macrophages. ApoE has been described as crucial in lipid metabolism but also as an important anti-inflammatory mediator regulating innate immunity and bone turnover. In the present study we investigated the role of Apo E in bone destruction during ...

The microenvironment of osteolytic metastases includes carcinoma cells derived from the primary lesion as well as bone-forming and bone-resorbing cells, namely osteoblasts (OB) and osteoclasts (OC). At this site, both the high glycolysis of cancer cells, and the bone resorption process result in a very acidic milieu. This, in turn, induces the surrounding stroma and OB to secrete pro-inflammatory cytokines and growth factors that promote tumorigenesis and cancer-associated ost...

An increasing amount of scientific evidence suggests that western diet is a risk factor for osteopenia and osteoporosis. Indeed, metabolic acidosis, occurring after high levels of protein intake, may adversely impact on the skeleton by disrupting calcium metabolism, and leads to a decrease of bone mineral density (BMD). Currently, the prevention and treatment of osteopenia and osteoporosis are mainly based on lifestyle modifications (i.e. exercise, quitting smoking and ensurin...