136 results on '"Silvia Colucci"'
Search Results
2. S284: HEPATOCYTE TOLL-LIKE RECEPTORS MEDIATE THE HEPCIDIN INFLAMMATORY RESPONSE TO PATHOGENS AND PATHOGEN-DERIVED LIGANDS
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Katharina Bonitz, Silvia Colucci, Richard Sparla, Ruiyue Qiu, Sandro Altamura, Katja Muedder, Stefan Zimmermann, Martina U. Muckenthaler, and Oriana Marques
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. LIGHT/TNFSF14 Affects Adipose Tissue Phenotype
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Angela Oranger, Graziana Colaianni, Giuseppe Ingravallo, Vincenza Sara Scarcella, Maria Felicia Faienza, Maria Grano, Silvia Colucci, and Giacomina Brunetti
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LIGHT/TNFSF14 ,high fat diet ,adipose tissue ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
LIGHT/TNFSF14 is linked to several signaling pathways as a crucial member of a larger immunoregulatory network. It is primarily expressed in inflammatory effector cells, and high levels of LIGHT have been reported in obesity. Thus, with the aim of deepening the knowledge of the role of LIGHT on adipose tissue phenotype, we studied wild-type (WT), Tnfsf14−/−, Rag−/− and Rag-/Tnfsf14- (DKO) mice fed a normal diet (ND) or high-fat diet (HFD). Our results show that, although there is no significant weight gain between the mice with different genotypes, it is significant within each of them. We also detected an increase in visceral White Adipose Tissue (vWAT) weight in all mice fed HFD, together with the lowest levels of vWAT weight in Tnfsf14−/− and DKO mice fed ND with respect to the other strain. Inguinal WAT (iWAT) weight is significantly affected by genotype and HFD. The least amount of iWAT was detected in DKO mice fed ND. Histological analysis of vWAT showed that both the genotype and the diet significantly affect the adipocyte area, whereas the number is affected only by the genotype. In iWAT, the genotype and the diet significantly affect mean adipocyte area and number; interestingly, the area with the least adipocyte was detected in DKO mice fed ND, suggesting a potential browning effect due to the simultaneous lack of mature lymphocytes and LIGHT. Consistently, Uncoupling Protein 1 (UCP1) staining of iWAT demonstrated that few positive brown adipocytes appeared in DKO mice. Furthermore, LIGHT deficiency is associated with greater levels of UCP1, highlighting the lack of its expression in Rag−/− mice. Liver examination showed that all mice fed HFD had a steatotic liver, but it was particularly evident for DKO mice. In conclusion, our study demonstrates that the adipose tissue phenotype is affected by LIGHT levels but also much more by mature lymphocytes.
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- 2024
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4. Iron-dependent BMP6 Regulation in Liver Sinusoidal Endothelial Cells Is Instructed by Hepatocyte-derived Secretory Signals
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Silvia Colucci, Sandro Altamura, Oriana Marques, Katja Müdder, Anand R. Agarvas, Matthias W. Hentze, and Martina U. Muckenthaler
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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5. Irisin Protects against Loss of Trabecular Bone Mass and Strength in Adult Ovariectomized Mice by Stimulating Osteoblast Activity
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Giuseppina Storlino, Manuela Dicarlo, Roberta Zerlotin, Patrizia Pignataro, Lorenzo Sanesi, Clelia Suriano, Angela Oranger, Giorgio Mori, Giovanni Passeri, Silvia Colucci, Maria Grano, and Graziana Colaianni
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Ovx-mice ,irisin ,bone loss ,estrogen ,subchondral bone ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Irisin is a peptide secreted by skeletal muscle that plays a major role in bone metabolism. Experiments in mouse models have shown that administration of recombinant irisin prevents disuse-induced bone loss. In this study, we aimed to evaluate the effects of irisin treatment for the prevention of bone loss in the ovariectomized (Ovx) mouse, the animal model commonly used to investigate osteoporosis caused by estrogen deficiency. Micro-Ct analysis conducted on Sham mice (Sham-veh) and Ovx mice treated with vehicle (Ovx-veh) or recombinant irisin (Ovx-irisn) showed bone volume fraction (BV/TV) decreases in femurs (Ovx-veh 1.39± 0.71 vs. Sham-veh 2.84 ± 1.23; p = 0.02) and tibia at both proximal condyles (Ovx-veh 1.97 ± 0.68 vs. Sham-veh 3.48 ± 1.26; p = 0.03) and the subchondral plate (Ovx-veh 6.33 ± 0.36 vs. Sham-veh 8.18 ± 0.41; p = 0.01), which were prevented by treatment with a weekly dose of irisin for 4 weeks. Moreover, histological analysis of trabecular bone showed that irisin increased the number of active osteoblasts per bone perimeter (Ovx-irisin 32.3 ± 3.9 vs. Ovx-veh 23.5 ± 3.6; p = 0.01), while decreasing osteoclasts (Ovx-irisin 7.6 ± 2.4 vs. Ovx-veh 12.9 ± 3.04; p = 0.05). The possible mechanism by which irisin enhances osteoblast activity in Ovx mice is upregulation of the transcription factor Atf4, one of the key markers of osteoblast differentiation, and osteoprotegerin, thereby inhibiting osteoclast formation.
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- 2023
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6. Short-Term Irisin Treatment Enhanced Neurotrophin Expression Differently in the Hippocampus and the Prefrontal Cortex of Young Mice
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Manuela Dicarlo, Patrizia Pignataro, Roberta Zerlotin, Clelia Suriano, Chiara Zecca, Maria Teresa Dell’Abate, Giuseppina Storlino, Angela Oranger, Lorenzo Sanesi, Giorgio Mori, Maria Grano, Graziana Colaianni, and Silvia Colucci
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depression ,antidepressant ,irisin ,fibronectin type III domain containing 5 ,physical exercise ,BDNF ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
As a result of physical exercise, muscle releases multiple exerkines, such as “irisin”, which is thought to induce pro-cognitive and antidepressant effects. We recently demonstrated in young healthy mice the mitigation of depressive behaviors induced by consecutive 5 day irisin administration. To understand which molecular mechanisms might be involved in such effect, we here studied, in a group of mice previously submitted to a behavioral test of depression, the gene expression of neurotrophins and cytokines in the hippocampus and prefrontal cortex (PFC), two brain areas frequently investigated in the depression pathogenesis. We found significantly increased mRNA levels of nerve growth factor (NGF) and fibroblast growth factor 2 (FGF-2) in the hippocampus and brain-derived growth factor (BDNF) in the PFC. We did not detect a difference in the mRNA levels of interleukin 6 (IL-6) and IL-1β in both brain regions. Except for BDNF in the PFC, two-way ANOVA analysis did not reveal sex differences in the expression of the tested genes. Overall, our data evidenced a site-specific cerebral modulation of neurotrophins induced by irisin treatment in the hippocampus and the PFC, contributing to the search for new antidepressant treatments targeted at single depressive events with short-term protocols.
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- 2023
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7. Once-Daily Subcutaneous Irisin Administration Mitigates Depression- and Anxiety-like Behavior in Young Mice
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Patrizia Pignataro, Manuela Dicarlo, Clelia Suriano, Lorenzo Sanesi, Roberta Zerlotin, Giuseppina Storlino, Angela Oranger, Chiara Zecca, Maria Teresa Dell’Abate, Giorgio Mori, Maria Grano, Silvia Colucci, and Graziana Colaianni
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antidepressant ,anxiolytic ,irisin ,subcutaneous injection ,young mice ,open field test ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Major depression is one of the most common psychiatric disorders worldwide, usually associated with anxiety. The multi-etiological nature of depression has increased the search for new antidepressant molecules, including irisin, for which, in a previous study, we tested its effect in young mice when administered intraperitoneally in a long-term intermittent manner. Here, we evaluated the effect of subcutaneous short-term irisin administration (100 µg/Kg/day/5 days) in male and female mice subjected to behavioral paradigms: Tail Suspension Test (TST), Forced Swim Test (FST), Elevated Plus Maze (EPM), and Y Maze (YM). Moreover, a qRT-PCR assay was performed to analyze the impact of irisin treatment on Pgc-1α/FNDC5 expression in the brain. A significant reduction in immobility time in TST and FST was observed in irisin-treated mice. Furthermore, irisin treatment significantly increased the number of entries and time spent in open arms, demonstrating its anxiolytic effect. Memory-enhancing effects were not reported in YM. Interestingly, no gender differences were observed in all behavioral tests. Overall, these results suggest that short-term subcutaneous irisin administration can exert an antidepressant and anxiolytic role, probably due to the activation of the Pgc-1α/FNDC5 system in the brain. Further investigation could lead to the identification of irisin as a new agent for the treatment of psychiatric disorders.
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- 2023
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8. Vitamin D Increases Irisin Serum Levels and the Expression of Its Precursor in Skeletal Muscle
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Lorenzo Sanesi, Manuela Dicarlo, Patrizia Pignataro, Roberta Zerlotin, Flavia Pugliese, Carla Columbu, Vincenzo Carnevale, Silvia Tunnera, Alfredo Scillitani, Maria Grano, Graziana Colaianni, and Silvia Colucci
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irisin ,vitamin D ,myoblast ,hyperparathyroidism ,Pgc1α ,Sirt1 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Irisin is a myokine synthesized by skeletal muscle, which performs key actions on whole-body metabolism. Previous studies have hypothesized a relationship between irisin and vitamin D, but the pathway has not been thoroughly investigated. The purpose of the study was to evaluate whether vitamin D supplementation affected irisin serum levels in a cohort of 19 postmenopausal women with primary hyperparathyroidism (PHPT) treated with cholecalciferol for six months. In parallel, to understand the possible link between vitamin D and irisin, we analyzed the expression of the irisin precursor, Fndc5, in the C2C12 myoblast cell line treated with a biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Our results demonstrate that vitamin D supplementation resulted in a significant increase in irisin serum levels (p = 0.031) in PHPT patients. In vitro, we show that vitamin D treatment on myoblasts enhanced Fndc5 mRNA after 48 h (p = 0.013), while it increased mRNAs of sirtuin 1 (Sirt1) (p = 0.041) and peroxisome proliferator-activated receptor γ coactivator 1α (Pgc1α) (p = 0.017) over a shorter time course. Overall, our data suggest that vitamin-D-induced modulation of Fndc5/irisin occurs through up-regulation of Sirt1, which together with Pgc1α, is an important regulator of numerous metabolic processes in skeletal muscle.
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- 2023
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9. Irisin Role in Chondrocyte 3D Culture Differentiation and Its Possible Applications
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Francesca Posa, Roberta Zerlotin, Anastasia Ariano, Michele Di Cosola, Graziana Colaianni, Aldo Di Fazio, Silvia Colucci, Maria Grano, and Giorgio Mori
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cartilage regeneration ,irisin ,human articular chondrocytes (HACs) ,3D pellet ,chondrogenesis ,Pharmacy and materia medica ,RS1-441 - Abstract
Irisin is a recently discovered cytokine, better known as an exercise-induced myokine, produced primarily in skeletal muscle tissue as a response to exercise. Although the skeleton was initially identified as the main target of Irisin, its action is also proving effective in many other tissues. Physical activity determines a series of beneficial effects on health, including the possibility of counteracting the damage that is caused by arthritis to the cartilage of people suffering from osteoarthritis. Nevertheless, up to now, the studies that have taken into consideration the possible involvement of Irisin on the well-being of cartilage tissue are particularly limited. In this study, we postulated that the protective effect of physical activity on cartilage tissue may depend on the paracrine action of Irisin secreted during exercise; therefore, we analyzed the effects of Irisin, in vitro, on chondrogenic differentiation. To achieve this goal, three-dimensional cultures of commercially available human articular chondrocytes (HACs) were treated with the molecule under study. Our results revealed new crosstalk mechanisms between muscle and cartilage tissue. Furthermore, the confirmation of Irisin ability to induce chondrogenic differentiation could favor the development of exercise-mimetic drugs, with application relevance for patients who cannot perform physical activity.
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- 2023
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10. Hfe Is Highly Expressed in Liver Sinusoidal Endothelial Cells But Is Not Needed to Maintain Systemic Iron Homeostasis In Vivo
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Silvia Colucci, Katja Müdder, Martina U. Muckenthaler, and Sandro Altamura
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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11. Irisin Modulates Inflammatory, Angiogenic, and Osteogenic Factors during Fracture Healing
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Angela Oranger, Roberta Zerlotin, Cinzia Buccoliero, Lorenzo Sanesi, Giuseppina Storlino, Ernestina Schipani, Kenneth Michael Kozloff, Giorgio Mori, Graziana Colaianni, Silvia Colucci, and Maria Grano
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fracture ,irisin ,TNFα ,MIP-1α ,VEGF ,MMP-13 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Bone fractures are a widespread clinical event due to accidental falls and trauma or bone fragility; they also occur in association with various diseases and are common with aging. In the search for new therapeutic strategies, a crucial link between irisin and bone fractures has recently emerged. To explore this issue, we subjected 8-week-old C57BL/6 male mice to tibial fracture, and then we treated them with intra-peritoneal injection of r-Irisin (100 µg/kg/weekly) or vehicle as control. At day 10 post fracture, histological analysis showed a significant reduced expression of inflammatory cytokines as tumor necrosis factor-alpha (TNFα) (p = 0.004) and macrophage inflammatory protein-alpha (MIP-1α) (p = 0.015) in the cartilaginous callus of irisin-treated mice compared to controls, supporting irisin’s anti-inflammatory role. We also found increased expressions of the pro-angiogenic molecule vascular endothelial growth factor (VEGF) (p = 0.002) and the metalloproteinase MMP-13 (p = 0.0006) in the irisin-treated mice compared to the vehicle ones, suggesting a myokine involvement in angiogenesis and cartilage matrix degradation processes. Moreover, the bone morphogenetic protein (BMP2) expression was also upregulated (p = 0.002). Taken together, our findings suggest that irisin can contribute to fracture repair by reducing inflammation and promoting vessel invasion, matrix degradation, and bone formation, supporting its possible role as a novel molecule for fracture treatment.
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- 2023
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12. Elevated Expression of ADAM10 in Skeletal Muscle of Patients with Idiopathic Inflammatory Myopathies Could Be Responsible for FNDC5/Irisin Unbalance
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Roberta Zerlotin, Marco Fornaro, Mariella Errede, Patrizia Pignataro, Clelia Suriano, Maddalena Ruggieri, Silvia Colucci, Florenzo Iannone, Maria Grano, and Graziana Colaianni
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irisin ,FNDC5 ,ADAM10 ,myopathy ,dermatomyositis ,immune-mediated necrotizing myopathy ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Dermatomyositis (DM) and immune-mediated necrotizing myopathy (IMNM) are two rare diseases belonging to the group of idiopathic inflammatory myopathies (IIM). Muscle involvement in DM is characterized by perifascicular atrophy and poor myofiber necrosis, while IMNM is characterized by myofiber necrosis with scarce inflammatory infiltrates. Muscle biopsies and laboratory tests are helpful in diagnosis, but currently, few biomarkers of disease activity and progression are available. In this context, we conducted a cohort study of forty-one DM and IMNM patients, aged 40–70 years. In comparison with control subjects, in the muscle biopsies of these patients, there was a lower expression of FNDC5, the precursor of irisin, a myokine playing a key role in musculoskeletal metabolism. Expectedly, the muscle cross-sectional areas of these patients were reduced, while, surprisingly, serum irisin levels were higher than in CTRL, as were mRNA levels of ADAM10, a metalloproteinase recently shown to be the cleavage agent for FNDC5. We hypothesize that elevated expression of ADAM10 in the skeletal muscle of DM and IMNM patients might be responsible for the discrepancy between irisin levels and FNDC5 expression. Future studies will be needed to understand the mechanisms underlying exacerbated FNDC5 cleavage and muscle irisin resistance in these inflammatory myopathies.
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- 2023
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13. Antidepressant Effect of Intermittent Long-Term Systemic Administration of Irisin in Mice
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Patrizia Pignataro, Manuela Dicarlo, Roberta Zerlotin, Giuseppina Storlino, Angela Oranger, Lorenzo Sanesi, Roberto Lovero, Cinzia Buccoliero, Giorgio Mori, Graziana Colaianni, Silvia Colucci, and Maria Grano
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depression ,antidepressant ,irisin ,FNDC5 ,physical exercise ,open field test ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Depression is a psychiatric disorder increasingly diffused worldwide. Evidence suggests that irisin, a myokine secreted by contracting muscle, mediates beneficial effects on several targets, including the brain. Here, the potential antidepressant properties of long-term intermittent systemic irisin administration (100 µg/kg/weekly for 1 month) were evaluated in mice by the Tail Suspension Test (TST), Forced Swim Test (FST), and Open Field Test (OFT). Furthermore, to deepen the molecular pathways underlying irisin treatment, the expression of irisin precursor, neurotrophic/growth factors, and cytokines was analyzed. Irisin treatment significantly decreased the immobility time in the TST and FST, suggesting an antidepressant effect. Additionally, irisin seemed to display an anxiolytic-like effect increasing the time spent in the OFT arena center. These findings were probably due to the modulation of endogenous brain factors as the gene expression of some neurotrophins, such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF-1), was upregulated only in irisin-treated mouse brain. Moreover, irisin modulated the expression of some cytokines (IL-1β, IL-4, IL-6, and IL-10). To the best of our knowledge, this is the first study demonstrating that the irisin antidepressant effect may be observed even with a systemic administration in mice. This could pave the way toward intriguing preclinical research in humans.
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- 2022
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14. LIGHT as regulator of bone homeostasis during osteolytic bone metastasis formation in non-small cell lung cancer patients
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Giacomina Brunetti, Dimas C. Belisario, Giuseppina Storlino, Graziana Colaianni, Lucio Buffoni, Giuseppe Ingravallo, Carl F. Ware, Silvia Colucci, Riccardo Ferracini, Maria Grano, and Ilaria Roato
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Diseases of the musculoskeletal system ,RC925-935 - Published
- 2020
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15. Irisin treatment prevents dysregulation of osteoblast differentiation and activity in 3D in vitro bone cocultures exposed to microgravity during the space flight CRS-14 mission
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Graziana Colaianni, Silvia Colucci, Giacomina Brunetti, Giorgio Mori, and Maria Grano
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Diseases of the musculoskeletal system ,RC925-935 - Published
- 2020
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16. Macrophage-HFE controls iron metabolism and immune responses in aged mice
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Naveen Kumar Tangudu, Dilay Yilmaz, Katharina Wörle, Andreas Gruber, Silvia Colucci, Kerstin Leopold, Martina U. Muckenthaler, and Maja Vujic Spasic
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2020
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17. Hemochromatosis proteins are dispensable for the acute hepcidin response to BMP2
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Alessia Pagani, Mariateresa Pettinato, Silvia Colucci, Alessandro Dulja, Martina Rauner, Antonella Nai, Clara Camaschella, Sandro Altamura, Martina U. Muckenthaler, and Laura Silvestri
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2020
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18. Iron-Related Parameters are Altered Between C57BL/6N and C57BL/6J Mus Musculus Wild-Type Substrains
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Oriana Marques, Joana Neves, Natalie K. Horvat, Silvia Colucci, Claudia Guida, and Martina U. Muckenthaler
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2019
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19. Effects of Sweet Cherry Polyphenols on Enhanced Osteoclastogenesis Associated With Childhood Obesity
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Filomena Corbo, Giacomina Brunetti, Pasquale Crupi, Sara Bortolotti, Giuseppina Storlino, Laura Piacente, Alessia Carocci, Alessia Catalano, Gualtiero Milani, Graziana Colaianni, Silvia Colucci, Maria Grano, Carlo Franchini, Maria Lisa Clodoveo, Gabriele D'Amato, and Maria Felicia Faienza
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obesity ,inflammation ,polyphenols ,sweet cherry ,osteoclastogenesis ,CD14+/CD16+ monocytes ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Childhood obesity is associated with the development of severe comorbidities, such as diabetes, cardiovascular diseases, and increased risk of osteopenia/osteoporosis and fractures. The status of low-grade inflammation associated to obesity can be reversed through an enhanced physical activity and by consumption of food enrich of anti-inflammatory compounds, such as omega-3 fatty acids and polyphenols. The aim of this study was to deepen the mechanisms of bone impairment in obese children and adolescents through the evaluation of the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs), and the assessment of the serum levels of RANKL and osteoprotegerin (OPG). Furthermore, we aimed to evaluate the in vitro effects of polyphenol cherry extracts on osteoclastogenesis, as possible dietary treatment to improve bone health in obese subjects. High RANKL levels were measured in obese with respect to controls (115.48 ± 35.20 pg/ml vs. 87.18 ± 17.82 pg/ml; p < 0.01), while OPG levels were significantly reduced in obese than controls (378.02 ± 61.15 pg/ml vs. 436.75 ± 95.53 pg/ml, respectively, p < 0.01). Lower Ad-SoS- and BTT Z-scores were measured in obese compared to controls (p < 0.05). A significant elevated number of multinucleated TRAP+ osteoclasts (OCs) were observed in the un-stimulated cultures of obese subjects compared to the controls. Interestingly, obese subjects displayed a higher percentage of CD14+/CD16+ than controls. Furthermore, in the mRNA extracts of obese subjects we detected a 2.5- and 2-fold increase of TNFα and RANKL transcripts compared to controls, respectively. Each extract of sweet cherries determined a dose-dependent reduction in the formation of multinucleated TRAP+ OCs. Consistently, 24 h treatment of obese PBMCs with sweet cherry extracts from the three cultivars resulted in a significant reduction of the expression of TNFα. In conclusion, the bone impairment in obese children and adolescents is sustained by a spontaneous osteoclastogenesis that can be inhibited in vitro by the polyphenol content of sweet cherries. Thus, our study opens future perspectives for the use of sweet cherry extracts, appropriately formulated as nutraceutical food, as preventive in healthy children and therapeutic in obese ones.
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- 2019
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20. Mechanisms Involved in Childhood Obesity-Related Bone Fragility
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Maria Felicia Faienza, Gabriele D'Amato, Mariangela Chiarito, Graziana Colaianni, Silvia Colucci, Maria Grano, Filomena Corbo, and Giacomina Brunetti
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osteoporosis ,low grade inflammation ,osteoimmunology ,osteoclast ,cytokines ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Childhood obesity is one of the major health problems in western countries. The excessive accumulation of adipose tissue causes inflammation, oxidative stress, apoptosis, and mitochondrial dysfunctions. Thus, obesity leads to the development of severe co-morbidities including type 2 diabetes mellitus, liver steatosis, cardiovascular, and neurodegenerative diseases which can develop early in life. Furthermore, obese children have low bone mineral density and a greater risk of osteoporosis and fractures. The knowledge about the interplay bone tissue and between adipose is still growing, although recent findings suggest that adipose tissue activity on bone can be fat-depot specific. Obesity is associated to a low-grade inflammation that alters the expression of adiponectin, leptin, IL-6, Monocyte Chemotactic Protein 1 (MCP1), TRAIL, LIGHT/TNFSF14, OPG, and TNFα. These molecules can affect bone metabolism, thus resulting in osteoporosis. The purpose of this review was to deepen the cellular mechanisms by which obesity may facilitate osteoporosis and bone fractures.
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- 2019
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21. The Myokine Irisin Promotes Osteogenic Differentiation of Dental Bud-Derived MSCs
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Francesca Posa, Graziana Colaianni, Michele Di Cosola, Manuela Dicarlo, Francesco Gaccione, Silvia Colucci, Maria Grano, and Giorgio Mori
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bone ,irisin ,osteocalcin ,mesenchymal stem cells (MSCs) ,precision medicine ,dental stem cells ,Biology (General) ,QH301-705.5 - Abstract
The myokine irisin, well known for its anabolic effect on bone tissue, has been demonstrated to positively act on osteoblastic differentiation processes in vitro. Mesenchymal stem cells (MSCs) have captured great attention in precision medicine and translational research for several decades due to their differentiation capacity, potent immunomodulatory properties, and their ability to be easily cultured and manipulated. Dental bud stem cells (DBSCs) are MSCs, isolated from dental tissues, that can effectively undergo osteoblastic differentiation. In this study, we analyzed, for the first time, the effects of irisin on DBSC osteogenic differentiation in vitro. Our results indicated that DBSCs were responsive to irisin, showed an enhanced expression of osteocalcin (OCN), a late marker of osteoblast differentiation, and displayed a greater mineral matrix deposition. These findings lead to deepening the mechanism of action of this promising molecule, as part of osteoblastogenesis process. Considering the in vivo studies of the effects of irisin on skeleton, irisin could improve bone tissue metabolism in MSC regenerative procedures.
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- 2021
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22. The Novel Role of PGC1α in Bone Metabolism
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Cinzia Buccoliero, Manuela Dicarlo, Patrizia Pignataro, Francesco Gaccione, Silvia Colucci, Graziana Colaianni, and Maria Grano
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mitochondria ,bone metabolism ,metabolic regulations ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) is a protein that promotes transcription of numerous genes, particularly those responsible for the regulation of mitochondrial biogenesis. Evidence for a key role of PGC1α in bone metabolism is very recent. In vivo studies showed that PGC1α deletion negatively affects cortical thickness, trabecular organization and resistance to flexion, resulting in increased risk of fracture. Furthermore, in a mouse model of bone disease, PGC1α activation stimulates osteoblastic gene expression and inhibits atrogene transcription. PGC1α overexpression positively affects the activity of Sirtuin 3, a mitochondrial nicotinammide adenina dinucleotide (NAD)-dependent deacetylase, on osteoblastic differentiation. In vitro, PGC1α overexpression prevents the reduction of mitochondrial density, membrane potential and alkaline phosphatase activity caused by Sirtuin 3 knockdown in osteoblasts. Moreover, PGC1α influences the commitment of skeletal stem cells towards an osteogenic lineage, while negatively affects marrow adipose tissue accumulation. In this review, we will focus on recent findings about PGC1α action on bone metabolism, in vivo and in vitro, and in pathologies that cause bone loss, such as osteoporosis and type 2 diabetes.
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- 2021
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23. FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective
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Patrizia Pignataro, Manuela Dicarlo, Roberta Zerlotin, Chiara Zecca, Maria Teresa Dell’Abate, Cinzia Buccoliero, Giancarlo Logroscino, Silvia Colucci, and Maria Grano
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irisin ,FNDC5 ,neuroinflammation ,neurodegeneration ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Irisin, the circulating peptide originating from fibronectin type III domain-containing protein 5 (FNDC5), is mainly expressed by muscle fibers under peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) control during exercise. In addition to several beneficial effects on health, physical activity positively affects nervous system functioning, particularly the hippocampus, resulting in amelioration of cognition impairments. Recently, FNDC5/irisin detection in hippocampal neurons and the presence of irisin in the cerebrospinal fluid opened a new intriguing chapter in irisin history. Interestingly, in the hippocampus of mice, exercise increases FNDC5 levels and upregulates brain-derived neurotrophic factor (BDNF) expression. BDNF, displaying neuroprotection and anti-inflammatory effects, is mainly produced by microglia and astrocytes. In this review, we discuss how these glial cells can morphologically and functionally switch during neuroinflammation by modulating the expression of a plethora of neuroprotective or neurotoxic factors. We also focus on studies investigating the irisin role in neurodegenerative diseases (ND). The emerging involvement of irisin as a mediator of the multiple positive effects of exercise on the brain needs further studies to better deepen this issue and the potential use in therapeutic approaches for neuroinflammation and ND.
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- 2021
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24. Osteogenic differentiation of mesenchymal stem cells from dental bud: Role of integrins and cadherins
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Adriana Di Benedetto, Giacomina Brunetti, Francesca Posa, Andrea Ballini, Felice Roberto Grassi, Graziana Colaianni, Silvia Colucci, Enzo Rossi, Elisabetta A. Cavalcanti-Adam, Lorenzo Lo Muzio, Maria Grano, and Giorgio Mori
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Mesenchymal stem cells ,Dental tissues ,Dental bud stem cells ,Osteogenic differentiation ,Cadherin ,Integrin ,Regenerative medicine ,Biology (General) ,QH301-705.5 - Abstract
Several studies have reported the beneficial effects of mesenchymal stem cells (MSCs) in tissue repair and regeneration. New sources of stem cells in adult organisms are continuously emerging; dental tissues have been identified as a source of postnatal MSCs. Dental bud is the immature precursor of the tooth, is easy to access and we show in this study that it can yield a high number of cells with ≥95% expression of mesenchymal stemness makers and osteogenic capacity. Thus, these cells can be defined as Dental Bud Stem Cells (DBSCs) representing a promising source for bone regeneration of stomatognathic as well as other systems. Cell interactions with the extracellular matrix (ECM) and neighboring cells are critical for tissue morphogenesis and architecture; such interactions are mediated by integrins and cadherins respectively. We characterized DBSCs for the expression of these adhesion receptors and examined their pattern during osteogenic differentiation. Our data indicate that N-cadherin and cadherin-11 were expressed in undifferentiated DBSCs and their expression underwent changes during the osteogenic process (decreasing and increasing respectively), while expression of E-cadherin and P-cadherin was very low in DBSCs and did not change during the differentiation steps. Such expression pattern reflected the mesenchymal origin of DBSCs and confirmed their osteoblast-like features. On the other hand, osteogenic stimulation induced the upregulation of single subunits, αV, β3, α5, and the formation of integrin receptors α5β1 and αVβ3. DBSCs differentiation toward osteoblastic lineage was enhanced when cells were grown on fibronectin (FN), vitronectin (VTN), and osteopontin (OPN), ECM glycoproteins which contain an integrin-binding sequence, the RGD motif. In addition we established that integrin αVβ3 plays a crucial role during the commitment of MSCs to osteoblast lineage, whereas integrin α5β1 seems to be dispensable. These data suggest that functionalization of biomaterials with such ECM proteins would improve bone reconstruction therapies starting from dental stem cells.
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- 2015
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25. Shedding 'LIGHT' on the Link between Bone and Fat in Obese Children and Adolescents
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Giacomina Brunetti, Maria Felicia Faienza, Laura Piacente, Giuseppina Storlino, Angela Oranger, Gabriele D'Amato, Gianpaolo De Filippo, Silvia Colucci, and Maria Grano
- Subjects
LIGHT/TNFSF14 ,obese subjects ,osteoclasts ,bone mineral density ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Obesity may affect bone health, but literature reports are contradictory about the correlation of body mass index (BMI) and bone markers. LIGHT, one of the immunostimulatory cytokines regulating the homeostasis of bone and adipose tissue, could be involved in obesity. The study involved 111 obese subjects (12.21 ± 3.71 years) and 45 controls. Patients underwent the evaluation of bone status by quantitative ultrasonography (QUS). LIGHT amounts were evaluated in sera by ELISA, whereas its expression on peripheral blood cells was evaluated by flow cytometry. Osteoclastogenesis was performed by culturing peripheral blood mononuclear cells (PBMCs) with or without anti-LIGHT antibodies. Obese patients showed significant high BMI-standard deviation score (SDS), weight-SDS, and Homeostatic model assessment for insulin resistance (HOMA-IR) that negatively correlated with the reduced Amplitude Dependent Speed of Sound (AD-SoS)-Z-score and Bone Transmission Time (BTT-Z)-score. They displayed significantly higher serum levels of LIGHT compared with controls (497.30 ± 363.45 pg/mL vs. 186.06 ± 101.41 pg/mL, p < 0.001). LIGHT expression on monocytes, CD3+-T-cells, and neutrophils was also higher in obese patients than in the controls. Finally, in PBMC cultures, the addition of anti-LIGHT antibodies induced a significant osteoclastogenesis inhibition. Our study highlighted the high serum levels of LIGHT in obese children and adolescents, and its relationship with both the grade of obesity and bone impairment.
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- 2020
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26. LIGHT/TNFSF14 as a New Biomarker of Bone Disease in Multiple Myeloma Patients Experiencing Therapeutic Regimens
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Giacomina Brunetti, Rita Rizzi, Giuseppina Storlino, Sara Bortolotti, Graziana Colaianni, Lorenzo Sanesi, Luciana Lippo, Maria Felicia Faienza, Anna Mestice, Paola Curci, Giorgina Specchia, Maria Grano, and Silvia Colucci
- Subjects
multiple myeloma ,bone disease ,LIGHT/TNFSF14 ,RANKL ,CD14+/CD16+ monocytes ,Immunologic diseases. Allergy ,RC581-607 - Abstract
We have previously shown that through the production of high LIGHT levels, immune cells contribute to both osteoclastogenesis and bone destruction in Multiple Myeloma (MM)-related bone disease. With the aim of further exploring the mechanisms underlying the development of MM-related bone disease, here we focused on a possible role of LIGHT in MM patients with active bone disease despite the treatment received. We detected LIGHT over-expression by circulating CD14+ monocytes from MM patients still showing active bone disease, despite the treatment. In addition, we found over-expression of receptor activator of nuclear factor kappa-B ligand (RANKL), whose pro-osteoclastogenic role is well-known, in T-lymphocytes isolated from the same patients. Although the percentages of circulating osteoclast progenitors, CD14+CD16+ monocytes, were higher in all the MM patients than in the controls spontaneous osteoclastogenesis occurred only in the cultures derived from PBMCs of MM patients with unresponsive bone disease. Of note, in the same cultures osteoclastogenesis was partially or completely inhibited, in a dose-dependent manner, by the addition of RANK-Fc or anti-LIGHT neutralizing antibody, demonstrating the contribution of both LIGHT and RANKL to the enhanced osteoclast formation observed. In addition, high serum levels of TRAP5b and CTX, the two markers of osteoclast activity, were detected in MM patients with bone disease not responsive to treatment. In conclusion, our study indicates a prominent role of LIGHT in the crosstalk among osteoclasts and immune cells, co-involved together with RANKL in the pathophysiological mechanisms leading to MM-related bone disease. This TNF superfamily member may thus be a possible new therapeutic target in MM-related bone disease.
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- 2018
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27. Irisin and Bone: From Preclinical Studies to the Evaluation of Its Circulating Levels in Different Populations of Human Subjects
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Graziana Colaianni, Lorenzo Sanesi, Giuseppina Storlino, Giacomina Brunetti, Silvia Colucci, and Maria Grano
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irisin ,osteoporosis ,sarcopenia ,Cytology ,QH573-671 - Abstract
Almost four years after the discovery of the anabolic action of irisin on bone in mice, ample clinical evidence is emerging in support of its additional physiological relevance in human bone. Irisin inversely correlates with sclerostin levels in adults with prediabetes and with vertebral fragility fractures in post-menopausal women. Furthermore, in athletes we observed a positive correlation between irisin and bone mineral density at different anatomical sites. Our group also described a positive association between serum irisin and bone status in healthy children and multivariate regression analysis showed that irisin is a stronger determinant of bone mineral status than bone alkaline phosphatase. In children with type 1 diabetes mellitus, serum irisin concentrations are positively associated with bone quality and with glycemic control following continuous subcutaneous insulin infusion. Additionally, our in vitro studies suggest the existence of a negative interplay between PTH and irisin biology and these results were also supported by the observation that post-menopausal women with primary hyperparathyroidism have lower levels of irisin compared to matched controls. In this review, we will focus on recent findings about circulating level of irisin in different populations of human subjects and its correlation with their bone status.
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- 2019
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28. 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
- Subjects
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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29. 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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30. Irisin Enhances Osteoblast Differentiation In Vitro
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Graziana Colaianni, Concetta Cuscito, Teresa Mongelli, Angela Oranger, Giorgio Mori, Giacomina Brunetti, Silvia Colucci, Saverio Cinti, and Maria Grano
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
It has been recently demonstrated that exercise activity increases the expression of the myokine Irisin in skeletal muscle, which is able to drive the transition of white to brown adipocytes, likely following a phenomenon of transdifferentiation. This new evidence supports the idea that muscle can be considered an endocrine organ, given its ability to target adipose tissue by promoting energy expenditure. In accordance with these new findings, we hypothesized that Irisin is directly involved in bone metabolism, demonstrating its ability to increase the differentiation of bone marrow stromal cells into mature osteoblasts. Firstly, we confirmed that myoblasts from mice subjected to 3 weeks of free wheel running increased Irisin expression compared to nonexercised state. The conditioned media (CM) collected from myoblasts of exercised mice induced osteoblast differentiation in vitro to a greater extent than those of mice housed in resting conditions. Furthermore, the differentiated osteoblasts increased alkaline phosphatase and collagen I expression by an Irisin-dependent mechanism. Our results show, for the first time, that Irisin directly targets osteoblasts, enhancing their differentiation. This finding advances notable perspectives in future studies which could satisfy the ongoing research of exercise-mimetic therapies with anabolic action on the skeleton.
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- 2014
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31. FSH and TSH in the Regulation of Bone Mass: The Pituitary/Immune/Bone Axis
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Graziana Colaianni, Concetta Cuscito, and Silvia Colucci
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Recent evidences have highlighted that the pituitary hormones have profound effects on bone, so that the pituitary-bone axis is now becoming an important issue in the skeletal biology. Here, we discuss the topical evidence about the dysfunction of the pituitary-bone axis that leads to osteoporotic bone loss. We will explore the context of FSH and TSH hormones arguing their direct or indirect role in bone loss. In addition, we will focus on the knowledge that both FSH and TSH have influence on proinflammatory and proosteoclastogenic cytokine expression, such as TNFα and IL-1, underlining the correlation of pituitary-bone axis to the immune system.
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- 2013
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32. Periodontal Disease: Linking the Primary Inflammation to Bone Loss
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Adriana Di Benedetto, Isabella Gigante, Silvia Colucci, and Maria Grano
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Periodontal disease (PD), or periodontitis, is defined as a bacterially induced disease of the tooth-supporting (periodontal) tissues. It is characterized by inflammation and bone loss; therefore understanding how they are linked would help to address the most efficacious therapeutic approach. Bacterial infection is the primary etiology but is not sufficient to induce the disease initiation or progression. Indeed, bacteria-derived factors stimulate a local inflammatory reaction and activation of the innate immune system. The innate response involves the recognition of microbial components by host cells, and this event is mediated by toll-like receptors (TLRs) expressed by resident cells and leukocytes. Activation of these cells leads to the release of proinflammatory cytokines and recruitment of phagocytes and lymphocytes. Activation of T and B cells initiates the adaptive immunity with Th1 Th2 Th17 Treg response and antibodies production respectively. In this inflammatory scenario, cytokines involved in bone regulation and maintenance have considerable relevance because tissue destruction is believed to be the consequence of host inflammatory response to the bacterial challenge. In the present review, we summarize host factors including cell populations, cytokines, and mechanisms involved in the destruction of the supporting tissues of the tooth and discuss treatment perspectives based on this knowledge.
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- 2013
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33. 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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34. IL-7 up-regulates TNF-alpha-dependent osteoclastogenesis in patients affected by solid tumor.
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Ilaria Roato, Giacomina Brunetti, Eva Gorassini, Maria Grano, Silvia Colucci, Lisa Bonello, Lucio Buffoni, Roberto Manfredi, Enrico Ruffini, Davide Ottaviani, Libero Ciuffreda, Antonio Mussa, and Riccardo Ferracini
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Medicine ,Science - Abstract
BACKGROUND: Interleukin-7 (IL-7) is a potent regulator of lymphocyte development, which has also significant effects on bone; in fact it is a potent osteoclastogenic factor. Some human solid tumors produce high IL-7 levels, suggesting a potential IL-7 role on tumor development and progression. METHODOLOGY: We studied 50 male patients affected by solid tumors, and their blood samples were collected at tumor diagnosis. PBMCs were isolated and cultured with/without IL-7 to study its influence on osteoclastogenesis. Serum and cell culture supernatant IL-7 levels were measured by ELISA. The quantitative analysis of IL-7 expression on T and B cells was performed by Real-Time PCR. PRINCIPAL FINDINGS: Serum IL-7 levels were highest in osteolytic cancer patients, followed by cancer patients without bone lesions, and then healthy controls. We showed the IL-7 production in PBMC cultures and particularly in monocyte and B cell co-cultures. A quantitative analysis of IL-7 expression in T and B cells confirmed that B cells had a high IL-7 expression. In all cell culture conditions, IL-7 significantly increased osteoclastogenesis and an anti-IL-7 antibody inhibited it. We demonstrated that IL-7 supports OC formation by inducing the TNF-alpha production and low RANKL levels, which synergize in promoting osteoclastogenesis. CONCLUSIONS: We demonstrated the presence of high serum IL-7 levels in patients with bone metastasis, suggesting the use of serum IL-7 level as a clinical marker of disease progression and of bone involvement. Moreover, we showed the capability of IL-7 to stimulate spontaneous osteoclastogenesis of bone metastatic patients and to induce osteoclastogenesis in cancer patients without bone involvement. These findings add further details to the disclosure of the mechanisms controlling bone metastasis in solid tumors.
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- 2006
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35. Irisin Protects against Loss of Trabecular Bone Mass and Strength in Adult Ovariectomized Mice by Stimulating Osteoblast Activity
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Colaianni, Giuseppina Storlino, Manuela Dicarlo, Roberta Zerlotin, Patrizia Pignataro, Lorenzo Sanesi, Clelia Suriano, Angela Oranger, Giorgio Mori, Giovanni Passeri, Silvia Colucci, Maria Grano, and Graziana
- Subjects
Ovx-mice ,irisin ,bone loss ,estrogen ,subchondral bone - Abstract
Irisin is a peptide secreted by skeletal muscle that plays a major role in bone metabolism. Experiments in mouse models have shown that administration of recombinant irisin prevents disuse-induced bone loss. In this study, we aimed to evaluate the effects of irisin treatment for the prevention of bone loss in the ovariectomized (Ovx) mouse, the animal model commonly used to investigate osteoporosis caused by estrogen deficiency. Micro-Ct analysis conducted on Sham mice (Sham-veh) and Ovx mice treated with vehicle (Ovx-veh) or recombinant irisin (Ovx-irisn) showed bone volume fraction (BV/TV) decreases in femurs (Ovx-veh 1.39± 0.71 vs. Sham-veh 2.84 ± 1.23; p = 0.02) and tibia at both proximal condyles (Ovx-veh 1.97 ± 0.68 vs. Sham-veh 3.48 ± 1.26; p = 0.03) and the subchondral plate (Ovx-veh 6.33 ± 0.36 vs. Sham-veh 8.18 ± 0.41; p = 0.01), which were prevented by treatment with a weekly dose of irisin for 4 weeks. Moreover, histological analysis of trabecular bone showed that irisin increased the number of active osteoblasts per bone perimeter (Ovx-irisin 32.3 ± 3.9 vs. Ovx-veh 23.5 ± 3.6; p = 0.01), while decreasing osteoclasts (Ovx-irisin 7.6 ± 2.4 vs. Ovx-veh 12.9 ± 3.04; p = 0.05). The possible mechanism by which irisin enhances osteoblast activity in Ovx mice is upregulation of the transcription factor Atf4, one of the key markers of osteoblast differentiation, and osteoprotegerin, thereby inhibiting osteoclast formation.
- Published
- 2023
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36. <scp>FKBP12</scp> inhibits hepcidin expression by modulating <scp>BMP</scp> receptors interaction and ligand responsiveness in hepatocytes
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Mariateresa Pettinato, Alessandro Dulja, Silvia Colucci, Valeria Furiosi, Franca Fette, Andrea U. Steinbicker, Martina U. Muckenthaler, Antonella Nai, Alessia Pagani, and Laura Silvestri
- Subjects
Hematology - Published
- 2023
37. In-hospital cost-effectiveness analysis of open versus staged fenestrated/branched endovascular elective repair of thoracoabdominal aneurysms
- Author
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Luca Bertoglio, Andrea Melloni, Carlotta Bugna, Camilla Grignani, Daria Bucci, Emanuela Foglia, Roberto Chiesa, Anna Odone, Eleonora Bossi, Silvia Colucci, Dario La Fauci, Simone Salvati, Carlo Signorelli, and Giacomo Pietro Vigezzi
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Surgery ,Cardiology and Cardiovascular Medicine - Published
- 2023
38. Constitutional PIGA mutations cause a novel subtype of hemochromatosis in patients with neurologic dysfunction
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Lena Muckenthaler, Oriana Marques, Silvia Colucci, Joachim Kunz, Piotr Fabrowski, Thomas Bast, Sandro Altamura, Britta Höchsmann, Hubert Schrezenmeier, Monika Langlotz, Paulina Richter-Pechanska, Tobias Rausch, Nicole Hofmeister-Mielke, Nikolas Gunkel, Matthias W. Hentze, Andreas E. Kulozik, and Martina U. Muckenthaler
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Male ,Adolescent ,Mutation ,Immunology ,Humans ,Membrane Proteins ,Hemochromatosis ,Cell Biology ,Hematology ,Nervous System Diseases ,Child ,Biochemistry - Abstract
Muckenthaler et al describe a novel form of hemochromatosis caused by a constitutional PIGA mutation in 3 children with associated neurologic dysfunction. Hemochromatosis results from decreased hepcidin, which is regulated by HFE, hemojuvelin (HJV), and transferrin receptor 2. HJV is a glycosylphosphatidylinositol-linked protein, so PIGA mutation leads to decreased HJV expression. Interestingly, none of the children had evidence of paroxysmal nocturnal hemoglobinuria. The cause of the novel association with central nervous system manifestations remains to be elucidated.
- Published
- 2022
39. Impact of 10-day bed rest on serum levels of irisin and markers of musculoskeletal metabolism
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Angela Oranger, Giuseppina Storlino, Manuela Dicarlo, Roberta Zerlotin, Patrizia Pignataro, Lorenzo Sanesi, Marco Narici, Rado Pišot, Bostjan Simunič, Graziana Colaianni, Maria Grano, and Silvia Colucci
- Subjects
muscle atrophy ,celična senesenca ,bed rest ,cell senescence ,haptoglobin ,irisin ,myostatin ,sclerostin ,Biochemistry ,miostatin ,gibalna neaktivnost ,Genetics ,physical inactivity ,mišična atrofija ,Molecular Biology ,udc:612.74:796.01 ,Biotechnology ,sklerostin - Abstract
The bed rest (BR) is a ground-based model to simulate microgravity mimicking skeletal-muscle alterations as in spaceflight. Molecular coupling between bone and muscle might be involved in physiological and pathological conditions. Thus, the new myokine irisin and bone-muscle turnover markers have been studied during and after 10 days of BR. Ten young male individuals were subjected to 10 days of horizontal BR. Serum concentrations of irisin, myostatin, sclerostin, and haptoglobin were assessed, and muscle tissue gene expression on vastus lateralis biopsies was determined. During 10-days BR, we observed no significant fluctuation levels of irisin, myostatin, and sclerostin. Two days after BR (R+2), irisin serum levels significantly decreased while myostatin, sclerostin, and haptoglobin were significantly increased compared with BR0. Gene expression of myokines, inflammatory molecules, transcription factors, and markers of muscle atrophy and senescence on muscle biopsies were not altered, suggesting that muscle metabolism of young, healthy subjects is able to adapt to the hypomobility condition during 10-day BR. However, when subjects were divided according to irisin serum levels at BR9, muscle ring finger-1 mRNA expression was significantly lower in subjects with higher irisin serum levels, suggesting that this myokine may prevent the triggering of muscle atrophy. Moreover, the negative correlation between p21 mRNA and irisin at BR9 indicated a possible inhibitory effect of the myokine on the senescence marker. In conclusion, irisin could be a prognostic marker of hypomobility-induced muscle atrophy, and its serum levels could protect against muscle deterioration by preventing and/or delaying the expression of atrophy and senescence cellular markers.
- Published
- 2022
40. Total reflection X-ray fluorescence spectrometry for trace determination of iron and some additional elements in biological samples
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Andreas Gruber, Maja Vujic Spasic, Riccarda Müller, Silvia Colucci, Alessa Wagner, and Kerstin Leopold
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DDC 540 / Chemistry & allied sciences ,Liver tissues ,Manganese ,01 natural sciences ,Biochemistry ,Liver cells ,Analytical Chemistry ,Mice ,DDC 570 / Life sciences ,HUMAN HAIR ,Limit of Detection ,Sample preparation ,TXRF ANALYSIS ,Cells, Cultured ,0303 health sciences ,Totalreflexionsröntgenfluoreszenzanalyse ,HEALTHY TISSUES ,Verdauung ,Liver ,Metals ,ddc:540 ,Digestion ,Total reflection X-ray fluorescence spectrometry ,Research Paper ,QUANTITATION ,Materials science ,Iron ,chemistry.chemical_element ,X-ray fluorescence ,Zinc ,Mass spectrometry ,03 medical and health sciences ,ddc:570 ,WHOLE-BLOOD ,Calibration ,Animals ,Bone marrow-derived macrophages ,Iron trace analysis ,EXPOSURE ,Bone marrow–derived macrophages ,030304 developmental biology ,Detection limit ,Chromatography ,Macrophages ,010401 analytical chemistry ,Leberepithelzelle ,Spectrometry, X-Ray Emission ,0104 chemical sciences ,Trace Elements ,chemistry ,Biometal trace analysis ,MULTIELEMENT DETERMINATION ,Cattle ,Graphite furnace atomic absorption - Abstract
Trace elements are essential for life and their concentration in cells and tissues must be tightly maintained and controlled to avoid pathological conditions. Established methods to measure the concentration of trace elements in biological matrices often provide only single element information, are time-consuming, and require special sample preparation. Therefore, the development of straightforward and rapid analytical methods for enhanced, multi-trace element determination in biological samples is an important and raising field of trace element analysis. Herein, we report on the development and validation of a reliable method based on total reflection X-ray fluorescence (TXRF) analysis to precisely quantify iron and other trace metals in a variety of biological samples, such as the liver, parenchymal and non-parenchymal liver cells, and bone marrow–derived macrophages. We show that TXRF allows fast and simple one-point calibration by addition of an internal standard and has the potential of multi-element analysis in minute sample amounts. The method was validated for iron by recovery experiments in homogenates in a wide concentration range from 1 to 1600 μg/L applying well-established graphite furnace atomic absorption spectrometry (GFAAS) as a reference method. The recovery rate of 99.93 ± 0.14% reveals the absence of systematic errors. Furthermore, the standard reference material “bovine liver” (SRM 1577c, NIST) was investigated in order to validate the method for further biometals. Quantitative recoveries (92–106%) of copper, iron, zinc, and manganese prove the suitability of the developed method. The limits of detection for the minute sample amounts are in the low picogram range., publishedVersion
- Published
- 2020
41. Macrophage-HFE controls iron metabolism and immune responses in aged mice
- Author
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Andreas Gruber, Silvia Colucci, Martina U. Muckenthaler, Naveen Kumar Tangudu, Dilay Yilmaz, Kerstin Leopold, Maja Vujic Spasic, and Katharina Wörle
- Subjects
Mice, Knockout ,business.industry ,Iron ,Macrophages ,Immunity ,Hematology ,Metabolism ,medicine.disease ,Mice ,Immune system ,Liver ,Immunology ,Animals ,Macrophage ,Medicine ,Hemochromatosis ,Hemochromatosis Protein ,Letters to the Editor ,business - Published
- 2020
42. 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
- Subjects
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.
- Published
- 2020
43. Systemic Administration of Recombinant Irisin Accelerates Fracture Healing in Mice
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Tiziana Annese, Mariella Errede, Cinzia Buccoliero, Roberta Zerlotin, Graziana Colaianni, Lorenzo Sanesi, Mohd Parvez Khan, Silvia Colucci, Ernestina Schipani, Kenneth M. Kozloff, Manuela Dicarlo, and Maria Grano
- Subjects
Male ,medicine.medical_specialty ,QH301-705.5 ,muscle ,medicine.medical_treatment ,Intraperitoneal injection ,chondrocytes ,Osteoclasts ,Bone healing ,bone ,Catalysis ,Article ,Inorganic Chemistry ,Fractures, Bone ,Mice ,Osteoclast ,Osteogenesis ,Internal medicine ,medicine ,Animals ,Physical and Theoretical Chemistry ,Biology (General) ,Molecular Biology ,Endochondral ossification ,QD1-999 ,Spectroscopy ,Reduction (orthopedic surgery) ,Fracture Healing ,business.industry ,Cartilage ,Organic Chemistry ,General Medicine ,Recombinant Proteins ,Computer Science Applications ,Fibronectins ,Mice, Inbred C57BL ,Chemistry ,medicine.anatomical_structure ,Endocrinology ,fracture ,Callus ,Systemic administration ,business ,irisin - Abstract
To date, pharmacological strategies designed to accelerate bone fracture healing are lacking. We subjected 8-week-old C57BL/6 male mice to closed, transverse, mid-diaphyseal tibial fractures and treated them with intraperitoneal injection of a vehicle or r-irisin (100 µg/kg/weekly) immediately following fracture for 10 days or 28 days. Histological analysis of the cartilaginous callus at 10 days showed a threefold increase in Collagen Type X (p = 0.0012) and a reduced content of proteoglycans (40%, p = 0.0018). Osteoclast count within the callus showed a 2.4-fold increase compared with untreated mice (p = 0.026), indicating a more advanced stage of endochondral ossification of the callus during the early stage of fracture repair. Further evidence that irisin induced the transition of cartilage callus into bony callus was provided by a twofold reduction in the expression of SOX9 (p = 0.0058) and a 2.2-fold increase in RUNX2 (p = 0.0137). Twenty-eight days post-fracture, microCT analyses showed that total callus volume and bone volume were increased by 68% (p = 0.0003) and 67% (p = 0.0093), respectively, and bone mineral content was 74% higher (p = 0.0012) in irisin-treated mice than in controls. Our findings suggest that irisin promotes bone formation in the bony callus and accelerates the fracture repair process, suggesting a possible use as a novel pharmacologic modulator of fracture healing.
- Published
- 2021
44. Evaluation of serum concentration of Irisin and molecules affecting the musculoskeletal system after 10-day Bed Rest
- Author
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Angela Oranger, Graziana Colaianni, Giuseppina Storlino, Cinzia Buccoliero, Patrizia Pignataro, Roberta Zerlotin, Manuela Dicarlo, Lorenzo Sanesi, Rado Pišot, Maria Grano, and Silvia Colucci
- Subjects
Endocrinology, Diabetes and Metabolism ,Orthopedics and Sports Medicine - Published
- 2022
45. Core Cross-Linked Polymeric Micelles for Specific Iron Delivery: Inducing Sterile Inflammation in Macrophages
- Author
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Peter Blümler, Silvia Colucci, Oriana Marques, Svenja Morsbach, Federico Fenaroli, Matthias W. Hentze, Tobias A. Bauer, Sascha Schmitt, Sara Chocarro, Kaloian Koynov, Rocio Sotillo, Christina Mertens, Michaela Jung, Natalie K. Horvat, Luca M. Carrella, Martina U. Muckenthaler, and Matthias Barz
- Subjects
Polymers ,Iron ,Biomedical Engineering ,Macrophage polarization ,Iron oxide ,Pharmaceutical Science ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Biomaterials ,chemistry.chemical_compound ,Mice ,Immune system ,Dihydrolipoic acid ,Macrophage ,Animals ,Micelles ,Inflammation ,Macrophages ,021001 nanoscience & nanotechnology ,Controlled release ,0104 chemical sciences ,chemistry ,Biophysics ,0210 nano-technology ,Iron oxide nanoparticles ,Intracellular - Abstract
Iron is an essential co-factor for cellular processes. In the immune system, it can activate macrophages and represents a potential therapeutic for various diseases. To specifically deliver iron to macrophages, iron oxide nanoparticles are embedded in polymeric micelles of reactive polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine). Upon surface functionalization via dihydrolipoic acid, iron oxide cores act as crosslinker themselves and undergo chemoselective disulfide bond formation with the surrounding poly(S-ethylsulfonyl-l-cysteine) block, yielding glutathione-responsive core cross-linked polymeric micelles (CCPMs). When applied to primary murine and human macrophages, these nanoparticles display preferential uptake, sustained intracellular iron release, and induce a strong inflammatory response. This response is also demonstrated in vivo when nanoparticles are intratracheally administered to wild-type C57Bl/6N mice. Most importantly, the controlled release concept to deliver iron oxide in redox-responsive CCPMs induces significantly stronger macrophage activation than any other iron source at identical iron levels (e.g., Feraheme), directing to a new class of immune therapeutics.
- Published
- 2021
46. Liver Sinusoidal Endothelial Cells Suppress Bone Morphogenetic Protein 2 Production in Response to TGFβ Pathway Activation
- Author
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A Dropmann, Sandro Altamura, Natalie K. Horvat, Martina U. Muckenthaler, Silvia Colucci, Oriana Marques, Katja Müdder, Seddik Hammad, and Steven Dooley
- Subjects
Liver Cirrhosis ,Iron Overload ,Bone Morphogenetic Protein 6 ,Iron ,Bone Morphogenetic Protein 2 ,Bone morphogenetic protein ,Bone morphogenetic protein 2 ,Paracrine signalling ,Mice ,Hepcidins ,Hepcidin ,Transforming Growth Factor beta ,Drug Discovery ,Hepatic Stellate Cells ,Animals ,Homeostasis ,Autocrine signalling ,Hepatology ,biology ,Chemistry ,Endothelial Cells ,Cell biology ,Bone morphogenetic protein 6 ,Gene Expression Regulation ,Hereditary hemochromatosis ,biology.protein ,Hepatic stellate cell ,Hepatocytes ,Signal Transduction - Abstract
BACKGROUND AND AIMS TGFβ/bone morphogenetic protein (BMP) signaling in the liver plays a critical role in liver disease. Growth factors, such as BMP2, BMP6, and TGFβ1, are released from LSECs and signal in a paracrine manner to hepatocytes and hepatic stellate cells to control systemic iron homeostasis and fibrotic processes, respectively. The misregulation of the TGFβ/BMP pathway affects expression of the iron-regulated hormone hepcidin, causing frequent iron overload and deficiency diseases. However, whether LSEC-secreted factors can act in an autocrine manner to maintain liver homeostasis has not been addressed so far. APPROACH AND RESULTS We analyzed publicly available RNA-sequencing data of mouse LSECs for ligand-receptor interactions and identified members of the TGFβ family (BMP2, BMP6, and TGFβ1) as ligands with the highest expression levels in LSECs that may signal in an autocrine manner. We next tested the soluble factors identified through in silico analysis in optimized murine LSEC primary cultures and mice. Exposure of murine LSEC primary cultures to these ligands shows that autocrine responses to BMP2 and BMP6 are blocked despite high expression levels of the required receptor complexes partially involving the inhibitor FK-506-binding protein 12. By contrast, LSECs respond efficiently to TGFβ1 treatment, which causes reduced expression of BMP2 through activation of activin receptor-like kinase 5. CONCLUSIONS These findings reveal that TGFβ1 signaling is functionally interlinked with BMP signaling in LSECs, suggesting druggable targets for the treatment of iron overload diseases associated with deficiency of the BMP2-regulated hormone hepcidin, such as hereditary hemochromatosis, β-thalassemia, and chronic liver diseases.
- Published
- 2021
47. The Novel Role of PGC1α in Bone Metabolism
- Author
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P Pignataro, Manuela Dicarlo, Maria Grano, Cinzia Buccoliero, Francesco Gaccione, Graziana Colaianni, and Silvia Colucci
- Subjects
0301 basic medicine ,Bone disease ,QH301-705.5 ,Adipose tissue ,Review ,Mitochondrion ,Osteocytes ,Catalysis ,Bone and Bones ,Bone remodeling ,Inorganic Chemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Osteogenesis ,Sirtuin 3 ,Coactivator ,medicine ,Animals ,Humans ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Spectroscopy ,Gene knockdown ,Organelle Biogenesis ,Osteoblasts ,biology ,Chemistry ,Organic Chemistry ,Cell Differentiation ,General Medicine ,medicine.disease ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Computer Science Applications ,Cell biology ,Mitochondria ,030104 developmental biology ,Mitochondrial biogenesis ,Sirtuin ,biology.protein ,bone metabolism ,metabolic regulations ,030217 neurology & neurosurgery ,Signal Transduction ,Transcription Factors - Abstract
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) is a protein that promotes transcription of numerous genes, particularly those responsible for the regulation of mitochondrial biogenesis. Evidence for a key role of PGC1α in bone metabolism is very recent. In vivo studies showed that PGC1α deletion negatively affects cortical thickness, trabecular organization and resistance to flexion, resulting in increased risk of fracture. Furthermore, in a mouse model of bone disease, PGC1α activation stimulates osteoblastic gene expression and inhibits atrogene transcription. PGC1α overexpression positively affects the activity of Sirtuin 3, a mitochondrial nicotinammide adenina dinucleotide (NAD)-dependent deacetylase, on osteoblastic differentiation. In vitro, PGC1α overexpression prevents the reduction of mitochondrial density, membrane potential and alkaline phosphatase activity caused by Sirtuin 3 knockdown in osteoblasts. Moreover, PGC1α influences the commitment of skeletal stem cells towards an osteogenic lineage, while negatively affects marrow adipose tissue accumulation. In this review, we will focus on recent findings about PGC1α action on bone metabolism, in vivo and in vitro, and in pathologies that cause bone loss, such as osteoporosis and type 2 diabetes.
- Published
- 2021
48. FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective
- Author
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Cinzia Buccoliero, Giancarlo Logroscino, Chiara Zecca, Silvia Colucci, Maria Teresa Dell'Abate, Roberta Zerlotin, Manuela Dicarlo, Maria Grano, and P Pignataro
- Subjects
Neuroimmunomodulation ,Models, Neurological ,Hippocampus ,FNDC5 ,Review ,Neuroprotection ,Catalysis ,neuroinflammation ,lcsh:Chemistry ,Inorganic Chemistry ,Mice ,Mediator ,Neurotrophic factors ,Physical Conditioning, Animal ,Medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,lcsh:QH301-705.5 ,Molecular Biology ,Exercise ,Spectroscopy ,Neuroinflammation ,Inflammation ,Microglia ,business.industry ,Brain-Derived Neurotrophic Factor ,Organic Chemistry ,Neurodegeneration ,neurodegeneration ,Neurodegenerative Diseases ,General Medicine ,medicine.disease ,Computer Science Applications ,Fibronectins ,medicine.anatomical_structure ,lcsh:Biology (General) ,lcsh:QD1-999 ,business ,Neuroscience ,irisin - Abstract
Irisin, the circulating peptide originating from fibronectin type III domain-containing protein 5 (FNDC5), is mainly expressed by muscle fibers under peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) control during exercise. In addition to several beneficial effects on health, physical activity positively affects nervous system functioning, particularly the hippocampus, resulting in amelioration of cognition impairments. Recently, FNDC5/irisin detection in hippocampal neurons and the presence of irisin in the cerebrospinal fluid opened a new intriguing chapter in irisin history. Interestingly, in the hippocampus of mice, exercise increases FNDC5 levels and upregulates brain-derived neurotrophic factor (BDNF) expression. BDNF, displaying neuroprotection and anti-inflammatory effects, is mainly produced by microglia and astrocytes. In this review, we discuss how these glial cells can morphologically and functionally switch during neuroinflammation by modulating the expression of a plethora of neuroprotective or neurotoxic factors. We also focus on studies investigating the irisin role in neurodegenerative diseases (ND). The emerging involvement of irisin as a mediator of the multiple positive effects of exercise on the brain needs further studies to better deepen this issue and the potential use in therapeutic approaches for neuroinflammation and ND.
- Published
- 2021
49. Hemochromatosis proteins are dispensable for the acute hepcidin response to BMP2
- Author
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Clara Camaschella, Silvia Colucci, Martina Rauner, Antonella Nai, Laura Silvestri, Alessia Pagani, Martina U. Muckenthaler, Alessandro Dulja, Mariateresa Pettinato, and Sandro Altamura
- Subjects
biology ,business.industry ,Histocompatibility Antigens Class I ,Bone Morphogenetic Protein 2 ,Hematology ,medicine.disease ,Bone morphogenetic protein 2 ,Hepcidins ,Hepcidin ,Immunology ,medicine ,biology.protein ,Humans ,Hemochromatosis ,business ,Hemochromatosis Protein ,Letters to the Editor - Published
- 2020
50. Shedding 'LIGHT' on the Link between Bone and Fat in Obese Children and Adolescents
- Author
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Silvia Colucci, Angela Oranger, Laura Piacente, Gabriele D'Amato, Maria Felicia Faienza, Giuseppina Storlino, Maria Grano, Gianpaolo De Filippo, and Giacomina Brunetti
- Subjects
0301 basic medicine ,Male ,Pediatric Obesity ,Adipose tissue ,Body Mass Index ,lcsh:Chemistry ,0302 clinical medicine ,Bone Density ,Osteogenesis ,LIGHT/TNFSF14 ,Child ,lcsh:QH301-705.5 ,Spectroscopy ,biology ,General Medicine ,Computer Science Applications ,Homeostatic model assessment ,Female ,Bone Remodeling ,Antibody ,medicine.medical_specialty ,Tumor Necrosis Factor Ligand Superfamily Member 14 ,Adolescent ,030209 endocrinology & metabolism ,Peripheral blood mononuclear cell ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Insulin resistance ,Internal medicine ,medicine ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,business.industry ,Organic Chemistry ,medicine.disease ,Obesity ,030104 developmental biology ,Endocrinology ,osteoclasts ,obese subjects ,lcsh:Biology (General) ,lcsh:QD1-999 ,Case-Control Studies ,biology.protein ,Leukocytes, Mononuclear ,Linear Models ,Insulin Resistance ,business ,bone mineral density ,Body mass index ,Homeostasis ,Biomarkers - Abstract
Obesity may affect bone health, but literature reports are contradictory about the correlation of body mass index (BMI) and bone markers. LIGHT, one of the immunostimulatory cytokines regulating the homeostasis of bone and adipose tissue, could be involved in obesity. The study involved 111 obese subjects (12.21 ±, 3.71 years) and 45 controls. Patients underwent the evaluation of bone status by quantitative ultrasonography (QUS). LIGHT amounts were evaluated in sera by ELISA, whereas its expression on peripheral blood cells was evaluated by flow cytometry. Osteoclastogenesis was performed by culturing peripheral blood mononuclear cells (PBMCs) with or without anti-LIGHT antibodies. Obese patients showed significant high BMI-standard deviation score (SDS), weight-SDS, and Homeostatic model assessment for insulin resistance (HOMA-IR) that negatively correlated with the reduced Amplitude Dependent Speed of Sound (AD-SoS)-Z-score and Bone Transmission Time (BTT-Z)-score. They displayed significantly higher serum levels of LIGHT compared with controls (497.30 ±, 363.45 pg/mL vs. 186.06 ±, 101.41 pg/mL, p <, 0.001). LIGHT expression on monocytes, CD3+-T-cells, and neutrophils was also higher in obese patients than in the controls. Finally, in PBMC cultures, the addition of anti-LIGHT antibodies induced a significant osteoclastogenesis inhibition. Our study highlighted the high serum levels of LIGHT in obese children and adolescents, and its relationship with both the grade of obesity and bone impairment.
- Published
- 2020
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