21 results on '"Giacomina Brunetti"'
Search Results
2. Vitamin D Promotes MSC Osteogenic Differentiation Stimulating Cell Adhesion and αVβ3 Expression
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Francesca Posa, Adriana Di Benedetto, Elisabetta A. Cavalcanti-Adam, Graziana Colaianni, Chiara Porro, Teresa Trotta, Giacomina Brunetti, Lorenzo Lo Muzio, Maria Grano, and Giorgio Mori
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Internal medicine ,RC31-1245 - Abstract
Vitamin D (Vit D) by means of its biological active form, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), has a protective effect on the skeleton by acting on calcium homeostasis and bone formation. Furthermore, Vit D has a direct effect on mesenchymal stem cells (MSCs) in stimulating their osteogenic differentiation. In this work, we present for the first time the effect of 1,25(OH)2D3 on MSC adhesion. Considering that cell adhesion to the substrate is fundamental for cell commitment and differentiation, we focused on the expression of αVβ3 integrin, which has a key role in the commitment of MSCs to the osteoblastic lineage. Our data indicate that Vit D increases αVβ3 integrin expression inducing the formation of focal adhesions (FAs). Moreover, we assayed MSC commitment in the presence of the extracellular matrix (ECM) glycoprotein fibronectin (FN), which is able to favor cell adhesion on surfaces and also to induce osteopontin (OPN) expression: this suggests that Vit D and FN synergize in supporting cell adhesion. Taken together, our findings provide evidence that Vit D can promote osteogenic differentiation of MSCs through the modulation of αVβ3 integrin expression and its subcellular organization, thus favoring binding with the matrix protein (FN).
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- 2018
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3. Vitamin D Effects on Osteoblastic Differentiation of Mesenchymal Stem Cells from Dental Tissues
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Francesca Posa, Adriana Di Benedetto, Graziana Colaianni, Elisabetta A. Cavalcanti-Adam, Giacomina Brunetti, Chiara Porro, Teresa Trotta, Maria Grano, and Giorgio Mori
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Internal medicine ,RC31-1245 - Abstract
1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D (Vit D), increases intestinal absorption of calcium and phosphate, maintaining a correct balance of bone remodeling. Vit D has an anabolic effect on the skeletal system and is key in promoting osteoblastic differentiation of human Mesenchymal Stem Cells (hMSCs) from bone marrow. MSCs can be also isolated from the immature form of the tooth, the dental bud: Dental Bud Stem Cells (DBSCs) are adult stem cells that can effectively undergo osteoblastic differentiation. In this work we investigated the effect of Vit D on DBSCs differentiation into osteoblasts. Our data demonstrate that DBSCs, cultured in an opportune osteogenic medium, differentiate into osteoblast-like cells; Vit D treatment stimulates their osteoblastic features, increasing the expression of typical markers of osteoblastogenesis like RUNX2 and Collagen I (Coll I) and, in a more important way, determining a higher production of mineralized matrix nodules.
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- 2016
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4. Bone-Immune Cell Crosstalk: Bone Diseases
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Giorgio Mori, Patrizia D’Amelio, Roberta Faccio, and Giacomina Brunetti
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma.
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- 2015
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5. Pathogenesis of Bone Diseases: The Role of Immune System
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Giacomina Brunetti, Giorgio Mori, Patrizia D’Amelio, and Roberta Faccio
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2015
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6. Human Myeloma Cell Lines Induce Osteoblast Downregulation of CD99 Which Is Involved in Osteoblast Formation and Activity
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Angela Oranger, Giacomina Brunetti, Claudia Carbone, Graziana Colaianni, Teresa Mongelli, Isabella Gigante, Roberto Tamma, Giorgio Mori, Adriana Di Benedetto, Marika Sciandra, Selena Ventura, Katia Scotlandi, Silvia Colucci, and Maria Grano
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Immunologic diseases. Allergy ,RC581-607 - Abstract
CD99 is a transmembrane glycoprotein expressed in physiological conditions by cells of different tissues, including osteoblasts (OBs). High or low CD99 levels have been detected in various pathological conditions, and the supernatant of some carcinoma cell lines can modulate CD99 expression in OB-like cells. In the present work we demonstrate for the first time that two different human myeloma cell lines (H929 and U266) and, in a less degree, their conditioned media significantly downregulate CD99 expression in normal human OBs during the differentiation process. In the same experimental conditions the OBs display a less differentiated phenotype as demonstrated by the decreased expression of RUNX2 and Collagen I. On the contrary, when CD99 was activated by using a specific agonist antibody, the OBs become more active as demonstrated by the upregulation of Alkaline Phosphatase, Collagen I, RUNX2, and JUND expression. Furthermore, we demonstrate that the activation of CD99 is able to induce the phosphorylation of ERK 1/2 and AKT intracellular signal transduction molecules in the OBs.
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- 2015
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7. Skeleton and Glucose Metabolism: A Bone-Pancreas Loop
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Maria Felicia Faienza, Vincenza Luce, Annamaria Ventura, Graziana Colaianni, Silvia Colucci, Luciano Cavallo, Maria Grano, and Giacomina Brunetti
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Bone has been considered a structure essential for mobility, calcium homeostasis, and hematopoietic function. Recent advances in bone biology have highlighted the importance of skeleton as an endocrine organ which regulates some metabolic pathways, in particular, insulin signaling and glucose tolerance. This review will point out the role of bone as an endocrine “gland” and, specifically, of bone-specific proteins, as the osteocalcin (Ocn), and proteins involved in bone remodeling, as osteoprotegerin, in the regulation of insulin function and glucose metabolism.
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- 2015
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8. The Crosstalk between the Bone and the Immune System: Osteoimmunology
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Giacomina Brunetti, Giorgio Mori, Patrizia D’Amelio, and Roberta Faccio
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2013
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9. The Interplay between the Bone and the Immune System
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Giorgio Mori, Patrizia D'Amelio, Roberta Faccio, and Giacomina Brunetti
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Immunologic diseases. Allergy ,RC581-607 - Abstract
In the last two decades, numerous scientists have highlighted the interactions between bone and immune cells as well as their overlapping regulatory mechanisms. For example, osteoclasts, the bone-resorbing cells, are derived from the same myeloid precursor cells that give rise to macrophages and myeloid dendritic cells. On the other hand, osteoblasts, the bone-forming cells, regulate hematopoietic stem cell niches from which all blood and immune cells are derived. Furthermore, many of the soluble mediators of immune cells, including cytokines and growth factors, regulate the activities of osteoblasts and osteoclasts. This increased recognition of the complex interactions between the immune system and bone led to the development of the interdisciplinary osteoimmunology field. Research in this field has great potential to provide a better understanding of the pathogenesis of several diseases affecting both the bone and immune systems, thus providing the molecular basis for novel therapeutic strategies. In these review, we reported the latest findings about the reciprocal regulation of bone and immune cells.
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- 2013
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10. The Role of TNF-α and TNF Superfamily Members in the Pathogenesis of Calcific Aortic Valvular Disease
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Antonella Galeone, Domenico Paparella, Silvia Colucci, Maria Grano, and Giacomina Brunetti
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Technology ,Medicine ,Science - Abstract
Calcific aortic valve disease (CAVD) represents a slowly progressive pathologic process associated with major morbidity and mortality. The process is characterized by multiple steps: inflammation, fibrosis, and calcification. Numerous studies focalized on its physiopathology highlighting different “actors” for the multiple “acts.” This paper focuses on the role of the tumor necrosis factor superfamily (TNFSF) members in the pathogenesis of CAVD. In particular, we discuss the clinical and experimental studies providing evidence of the involvement of tumor necrosis factor-alpha (TNF-α), receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL), its membrane receptor RANK and its decoy receptor osteoprotegerin (OPG), and TNF-related apoptosis-inducing ligand (TRAIL) in valvular calcification.
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- 2013
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11. LIGHT/TNFSF14 regulates estrogen deficiency‐induced bone loss
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Monica Celi, Giuseppina Storlino, Maria Grano, Giovanni Passeri, Angela Oranger, Carl F. Ware, Giacomina Brunetti, Graziana Colaianni, Silvia Colucci, Giuseppe Ingravallo, Maria Felicia Faienza, Janne E. Reseland, Mariasevera Di Comite, and Umberto Tarantino
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Adult ,0301 basic medicine ,Tumor Necrosis Factor Ligand Superfamily Member 14 ,medicine.medical_specialty ,Stromal cell ,Osteoimmunology ,medicine.medical_treatment ,TNF ,Bone Marrow Cells ,Pathology and Forensic Medicine ,postmenopausal osteoporosis ,Settore MED/33 ,Mice ,03 medical and health sciences ,immune cells ,0302 clinical medicine ,bone loss ,Osteoprotegerin ,Osteogenesis ,LIGHT/TNFSF14 ,Internal medicine ,Bone cell ,medicine ,Animals ,Humans ,Bone Resorption ,RANKL/OPG ,osteoimmunology ,B-Lymphocytes ,biology ,Chemistry ,RANK Ligand ,osteoblasts ,osteoclasts ,ovariectomy ,Cell Differentiation ,Estrogens ,Middle Aged ,030104 developmental biology ,Endocrinology ,Cytokine ,medicine.anatomical_structure ,RANKL ,030220 oncology & carcinogenesis ,biology.protein ,Tumor necrosis factor alpha ,Bone marrow ,Stromal Cells - Abstract
Bone loss induced by ovariectomy is due to the direct activity on bone cells and mesenchymal cells and to the dysregulated activity of bone marrow cells, including immune cells and stromal cells, but the underlying mechanisms are not completely known. Here, we demonstrate that ovariectomy induces the T-cell co-stimulatory cytokine LIGHT, which stimulates both osteoblastogenesis and osteoclastogenesis by modulating osteoclastogenic cytokine expression, including TNF, osteoprotegerin, and the receptor activator of nuclear factor-κB ligand (RANKL). Predictably, LIGHT-deficient (Tnfsf14-/- ) mice are protected from ovariectomy-dependent bone loss, whereas trabecular bone mass increases in mice deficient in both LIGHT and T and B lymphocytes (Rag -/- Tnfsf14 -/- ) and is associated with an inversion of the TNF and RANKL/OPG ratio. Furthermore, women with postmenopausal osteoporosis display high levels of LIGHT in circulating T cells and monocytes. Taken together, these results indicate that LIGHT mediates bone loss induced by ovariectomy, suggesting that patients with postmenopausal osteoporosis may benefit from LIGHT antagonism. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- Published
- 2020
12. LIGHT/TNFSF14 Promotes Osteolytic Bone Metastases in Non‐small Cell Lung Cancer Patients
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Giuseppe Ingravallo, Maria Felicia Faienza, Elisa Centini, Carl F. Ware, Dimas Carolina Belisario, Giuseppina Storlino, Riccardo Ferracini, Sara Bortolotti, Silvia Colucci, Silvia Novello, Giacomina Brunetti, Janne E. Reseland, Lorenzo Sanesi, Graziana Colaianni, Ilaria Roato, Claudia Voena, Giorgio Mori, Maria Grano, Rita Rizzi, Lucio Buffoni, Roberta Pulito, and Valentina Alliod
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0301 basic medicine ,Tumor Necrosis Factor Ligand Superfamily Member 14 ,Lung Neoplasms ,NON-SMALL CELL LUNG CANCER (NSCLC) ,Bone disease ,Endocrinology, Diabetes and Metabolism ,Osteoclasts ,non-small cell lung cancer (NSCLC) ,Bone Neoplasms ,030209 endocrinology & metabolism ,LIGHT (TNFSF14) ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Osteoclast ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Orthopedics and Sports Medicine ,BONE METASTASIS ,OSTEOCLAST ,Lung cancer ,biology ,business.industry ,RANK Ligand ,Bone metastasis ,medicine.disease ,030104 developmental biology ,Lymphatic system ,medicine.anatomical_structure ,RANKL ,Leukocytes, Mononuclear ,Cancer research ,biology.protein ,Tumor necrosis factor alpha ,business - Abstract
Tumor necrosis factor superfamily member 14 (TNFSF14), LIGHT, is a component of the cytokine network that regulates innate and adaptive immune responses, which promote homeostasis of lymphoid organs, liver, and bone. Metastatic tumors often disrupt the tissue microenvironment, thus altering the homeostasis of the invaded organ; however, the underlying mechanisms required further studies. We investigated the role of LIGHT in osteolytic bone disease induced by metastatic non-small cell lung cancer (NSCLC). Patients diagnosed with NSCLC bone metastasis show significantly higher levels of LIGHT expressed in monocytes compared with non-bone metastatic tumors and healthy controls. Serum LIGHT levels were also higher in patients with bone metastases than in controls, suggesting a role for LIGHT in stimulating osteoclast precursors. In bone metastatic patients, we also detected increased RNA expression and serum RANKL levels, thus by adding anti-LIGHT or RANK-fragment crystallizable region (RANK-Fc) in PBMC cultures, a significant inhibition of osteoclastogenesis was observed. To model this observation in mice, we used the mouse lung cancer cell line LLC-1. After intratibial implantation, wild-type mice showed an increased number of osteoclasts but reduced numbers of osteoblasts and decreased osteoid formation. In contrast, Tnfsf14-/- mice showed no significant bone loss or other changes in bone homeostasis associated with this model. These data indicate LIGHT is a key control mechanism for regulating bone homeostasis during metastatic invasion. Thus, LIGHT may be a novel therapeutic target in osteolytic bone metastases. © 2019 American Society for Bone and Mineral Research.
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- 2020
13. Unusual ultrasonographic finding of ovarian hyperstimulation syndrome in a preterm newborn with severe intra‐uterine growth retardation
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Maria Pia Natale, Maria Felicia Faienza, Elena D'Amato, Gabriele D'Amato, and Giacomina Brunetti
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medicine.medical_specialty ,Growth retardation ,Obstetrics ,business.industry ,Premature birth ,Pediatrics, Perinatology and Child Health ,medicine ,Ovarian hyperstimulation syndrome ,medicine.disease ,business ,Intra uterine - Published
- 2019
14. Impairment of Bone Remodeling inLIGHT/TNFSF14-Deficient Mice
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Luciana Lippo, Maria Grano, Janne E. Reseland, Giuseppe Ingravallo, Isabella Gigante, Adriana Di Benedetto, Mariasevera Di Comite, Angela Oranger, Giacomina Brunetti, Giovanni Passeri, Sara Bortolotti, Koji Tamada, Paolo Pignataro, Giuseppina Storlino, Ernestina Schipani, Giorgio Mori, Lindsay K. Ward-Kavanagh, Graziana Colaianni, Maria Felicia Faienza, Silvia Colucci, and Carl F. Ware
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musculoskeletal diseases ,0301 basic medicine ,medicine.medical_specialty ,Bone disease ,Chemistry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Osteoimmunology ,medicine.disease ,Bone remodeling ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Cytokine ,medicine.anatomical_structure ,Endocrinology ,Osteoprotegerin ,Osteoclast ,Internal medicine ,Bone cell ,medicine ,Orthopedics and Sports Medicine ,Cancellous bone ,030215 immunology - Abstract
Multiple cytokines produced by immune cells induce remodeling and aid in maintaining bone homeostasis through differentiation of bone-forming osteoblasts and bone-resorbing osteoclasts. Here, we investigate bone remodeling controlled by the tumor necrosis factor (TNF) superfamily cytokine LIGHT. LIGHT-deficient mice (Tnfsf14-/- ) exhibit spine deformity and reduced femoral cancellous bone mass associated with an increase in the osteoclast number and a slight decrease of osteoblasts compared with WT mice. The effect of LIGHT in bone cells can be direct or indirect, mediated by both the low expression of the anti-osteoclastogenic osteoprotegerin (OPG) in B and T cells and reduced levels of the pro-osteoblastogenic Wnt10b in CD8+ T cells in Tnfsf14-/- mice. LIGHT stimulation increases OPG levels in B, CD8+ T, and osteoblastic cells, as well as Wnt10b expression in CD8+ T cells. The high bone mass in Light and T- and B-cell-deficient mice (Rag- /Tnfsf14- ) supports the cooperative role of the immune system in bone homeostasis. These results implicate LIGHT as a potential target in bone disease. © 2017 American Society for Bone and Mineral Research.
- Published
- 2017
15. High serum sclerostin levels in children with haemophilia A
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Annamaria Ventura, Luciano Cavallo, Lucia Dora Notarangelo, Elena Santagostino, Matteo Luciani, Rosa M. Mura, Giuseppe Lassandro, Ilaria Lazzareschi, Giacomina Brunetti, Maria Grano, Laura Piacente, Maria Felicia Faienza, and Paola Giordano
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Genetic Markers ,Male ,musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Adolescent ,Sclerostin ,Haemophilia A ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,Hemophilia A ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Osteoprotegerin ,Bone Density ,hemic and lymphatic diseases ,Internal medicine ,Bone mineral density ,Humans ,Medicine ,Receptor activator of nuclear factor-κB ligand ,Child ,Preschool ,Receptor ,Adaptor Proteins, Signal Transducing ,Bone mineral ,Lumbar Vertebrae ,DKK1 ,business.industry ,Activator (genetics) ,Case-control study ,Hematology ,medicine.disease ,Endocrinology ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,chemistry ,Child, Preschool ,Case-Control Studies ,Bone Morphogenetic Proteins ,business ,human activities - Abstract
Keywords: sclerostin; haemophilia A; bone mineral density; receptor activator of nuclear factor-κB ligand; osteoprotegerin; DKK1
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- 2015
16. Sclerostin is overexpressed by plasma cells from multiple myeloma patients
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Giorgina Specchia, Erminia Rinaldi, Giacomina Brunetti, Angela Oranger, Rita Rizzi, Giorgio Mori, Maria Grano, Paola Curci, Alberta Zallone, and Silvia Colucci
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medicine.medical_specialty ,Osteolysis ,Bone disease ,General Neuroscience ,Wnt signaling pathway ,Osteoblast ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,medicine.anatomical_structure ,Endocrinology ,History and Philosophy of Science ,chemistry ,DKK1 ,Internal medicine ,medicine ,Sclerostin ,Bone marrow ,Multiple myeloma - Abstract
Sclerostin, an osteocyte-expressed negative regulator of bone formation, is one of the inhibitors of Wnt signaling that is a critical pathway in the correct process of osteoblast differentiation. It has been demonstrated that Wnt signaling through the secretion of Wnt inhibitors, such as DKK1, sFRP-2, and sFRP-3, plays a key role in the decreased osteoblast activity associated with multiple myeloma (MM) bone disease. We provide evidence that sclerostin is expressed by myeloma cells that are human myeloma cell lines and plasma cells (CD138(+) cells) obtained from the bone marrow (BM) of a large number of MM patients with bone disease. Moreover, we show that there are no differences in sclerostin serum levels between MM patients and controls. Thus, our data indicate that MM cells, as a sclerostin source in the BM, could create a microenvironment with high sclerostin concentration that could contribute toward inhibiting osteoblast differentiation.
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- 2011
17. Dental pulp stem cells: osteogenic differentiation and gene expression
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Giorgio Mori, Claudia Carbone, Lorenzo Lo Muzio, Angela Oranger, Andrea Ballini, Silvia Colucci, Felice Roberto Grassi, Maria Grano, C. Mori, and Giacomina Brunetti
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Regulation of gene expression ,JUNB ,General Neuroscience ,Mesenchymal stem cell ,Osteoblast ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell biology ,medicine.anatomical_structure ,stomatognathic system ,History and Philosophy of Science ,Dental pulp stem cells ,Immunology ,medicine ,Bone marrow ,Stem cell ,Adult stem cell - Abstract
Dental pulp stem cells (DPSCs) are an adult stem cell population with high proliferative potential and the ability to differentiate in many cell types, and this has led scientists to consider these cells to be an alternative source of postnatal stem cells comparable to mesenchymal stem cells from bone marrow. In this work, we studied the osteoblastic phenotype developed by DPSCs cultured in osteogenic medium. In particular, we analyzed the expression of the typical osteoblast markers such as alkaline phosphatase, collagen type I, osteocalcin, osteopontin, as well as mineralized matrix production. Furthermore, the gene expression during DPSC differentiation into osteoblastic cells was studied by microarray technology. Using microarray and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, we found that IGFBP-5, JunB, and NURR1 genes are upregulated during the differentiation of DPSCs. These data indicate that opportunely differentiated DPSCs show a correct osteoblastic phenotype. Therefore, during the osteoblastic differentiation process, IGFBP-5, JunB, and NURR1 gene expression is significantly increased.
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- 2011
18. The formation of osteoclasts in multiple myeloma bone disease patients involves the secretion of soluble decoy receptor 3
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Rita Rizzi, Alberta Zallone, Maria Grano, Silvia Colucci, Graziana Colaianni, Vincenzo Liso, Giacomina Brunetti, Angela Oranger, Giorgio Mori, and Matteo Centonze
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Genetically modified mouse ,medicine.medical_specialty ,Osteolysis ,Bone disease ,business.industry ,General Neuroscience ,T lymphocyte ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Endocrinology ,medicine.anatomical_structure ,History and Philosophy of Science ,Osteoclast ,Internal medicine ,medicine ,Bone marrow ,Decoy receptor 3 ,business ,Multiple myeloma - Abstract
Soluble decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, has recently been reported to increase osteoclast (OC) differentiation. Its impact on the skeleton was reinforced by a study on DcR3 transgenic mice showing a decreased bone mass through the elevation of OC number, providing some initial evidence of DcR3 involvement in bone diseases. In this study we show that malignant plasma cells and T lymphocytes from myeloma patients directly produce DcR3, and this molecule supports the elevated formation of OCs in both peripheral blood and bone marrow from the patients. We also show that serum DcR3 levels in myeloma patients are significantly higher compared to controls.
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- 2010
19. TRAIL Is Involved in Human Osteoclast Apoptosis
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Alberta Zallone, Giacomina Brunetti, Giorgio Mori, Felice Roberto Grassi, Silvia Colucci, Roberto Tamma, Adriana Di Benedetto, Angela Oranger, Maria Grano, and Paolo Pignataro
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General Neuroscience ,Osteoclasts ,Apoptosis ,Cell Differentiation ,Biology ,Microfilament ,General Biochemistry, Genetics and Molecular Biology ,Bone remodeling ,Cell biology ,TNF-Related Apoptosis-Inducing Ligand ,medicine.anatomical_structure ,History and Philosophy of Science ,Downregulation and upregulation ,Osteoclast ,Bone cell ,medicine ,Humans ,Viability assay ,Receptor ,Cells, Cultured - Abstract
Control of osteoclast (OC) apoptosis has been recognized as a critical regulatory factor in bone remodeling. TRAIL, a member of the TNF superfamily, induces apoptosis in neoplastic and normal cells. However, few data are available on the effects of TRAIL on bone cells, thus in the present study we investigated TRAIL role on the apoptosis of human mature OCs. We show that TRAIL treatment causes reduced cell viability, loss of nuclei integrity, and derangement of the actin microfilament in OCs. We also demonstrated that the death receptor DR5, upregulated by TRAIL, could be the mediator of TRAIL-induced OC apoptosis.
- Published
- 2007
20. IL-7 Modulates Osteoclastogenesis in Patients Affected by Solid Tumors
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Maria Grano, Giacomina Brunetti, Eva Gorassini, Libero Ciuffreda, Antonio Mussa, Riccardo Ferracini, and Ilaria Roato
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Male ,T-Lymphocytes ,Osteoclasts ,Clinical marker ,Enzyme-Linked Immunosorbent Assay ,Models, Biological ,Peripheral blood mononuclear cell ,General Biochemistry, Genetics and Molecular Biology ,History and Philosophy of Science ,Osteoclast ,Neoplasms ,medicine ,Humans ,In patient ,Neoplasm Metastasis ,Bone metastasis, IL-7, Osteoclast ,B-Lymphocytes ,IL-7 ,Dose-Response Relationship, Drug ,Tumor Necrosis Factor-alpha ,business.industry ,Interleukin-7 ,General Neuroscience ,Disease progression ,Bone metastasis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Case-Control Studies ,Immunology ,Disease Progression ,Leukocytes, Mononuclear ,business - Abstract
High levels of interleukin-7 (IL-7) have been associated with bone loss due to its stimulatory osteoclastogenic activity. Osteolytic patients' peripheral blood mononuclear cells (PBMCs) differentiate into osteoclasts without adding stimulating factors. Now, we investigated the potential role of IL-7 in the spontaneous osteoclastogenesis occurring in these patients. We identified significant differences in serum IL-7 levels between patients with/without bone metastases, suggesting that IL-7 might be effective as a clinical marker of disease progression. In patients' PBMC cultures we demonstrated that IL-7 stimulates osteoclastogenesis by inducing TNF-alpha release by T and B cells. These findings add further details to the disclosure of the mechanisms controlling bone metastases in solid tumors.
- Published
- 2007
21. Mechanisms of spontaneous osteoclastogenesis in cancer with bone involvement
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Ilaria Roato, Giacomina Brunetti, Maria Grano, Silvia Colucci, Riccardo Ferracini, Antonio Mussa, and Oscar Bertetto
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Genetic Markers ,Male ,Osteolysis ,Osteoclastogenesis ,T-Lymphocytes ,Gene Expression ,Osteoclasts ,Bone Neoplasms ,Biochemistry ,Peripheral blood mononuclear cell ,Osteoclast ,Genetics ,medicine ,Humans ,Bone Resorption ,Neoplasm Metastasis ,Bone ,Osteoclastogenesis, Cancer, Bone ,Molecular Biology ,Cells, Cultured ,Multiple myeloma ,Aged ,Cancer ,Aged, 80 and over ,biology ,business.industry ,Middle Aged ,medicine.disease ,Resorption ,Gene Expression Regulation, Neoplastic ,Phenotype ,medicine.anatomical_structure ,RANKL ,Immunology ,Leukocytes, Mononuclear ,biology.protein ,Female ,Antibody ,business ,Biotechnology - Abstract
Bone metastases represents a common cause of morbidity in patients suffering many types of cancer: breast, lung, kidney, prostate, and multiple myeloma. Osteolytic metastases often cause severe pain, pathologic fractures, hypercalcemia, spinal cord compression, and other nerve-compression syndromes. Osteoclasts (OCs), cells deriving from granulocitic-macrophagic lineage, are responsible for osteolysis, which may be reduced by inhibiting both OCs formation and activity. By studying bone osteolytic metastases mechanism in solid tumors, we report here our findings that cancer patients with bone involvement display an increase in osteoclasts precursors, compared with both healthy controls and cancer patients without bone metastases. Peripheral blood mononuclear cells (PBMCs) from patients with osteolytic lesions show osteoclastogenesis without adding M-CSF, RANKL, or TNF-alpha. However, these factors are necessary to generate OCs from healthy donors, non-osteolytic patient PBMCs and T-cell depleted PBMCs. OCs derived from cancer patients show more resorption pits than OCs from healthy donors and express genes involved in osteoclastogenesis. Our data show that a spontaneous osteoclastogenesis occurs in patients affected by osteolytic lesions and may be supported by factors released by T lymphocytes. These factors could give a priming to osteoclast precursors and promote osteoclastogenesis. In fact, T-cell depleted PBMCs do not differentiate into OCs without adding M-CSF and RANKL. Moreover, we do not obtain a higher number of OCs by increasing RANKL doses in cultures, and OCs and T lymphocytes mRNA level are detected for TNF-alpha but not for RANKL. The addition of OPG to PBMCs cultures do not modify spontaneous osteoclastogenesis. A neutralizing anti-TNF-alpha antibody in unstimulated PBMC cultures of osteolytic cancer patients induces an inhibition of osteoclastogenesis. These data suggest that TNF-alpha may be responsible for osteoclastogenesis in these tumors.
- Published
- 2004
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