41 results on '"Canciani B"'
Search Results
2. Epidermal growth factor signalling pathway in endochondral ossification: an evidence-based narrative review
- Author
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Mangiavini, L., primary, Peretti, G. M., additional, Canciani, B., additional, and Maffulli, N., additional
- Published
- 2021
- Full Text
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3. Epidermal growth factor signalling pathway in endochondral ossification: an evidence-based narrative review.
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Mangiavini, L., Peretti, G. M., Canciani, B., and Maffulli, N.
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EPIDERMAL growth factor ,ENDOCHONDRAL ossification ,CELLULAR signal transduction ,BONE growth ,TISSUE differentiation - Abstract
During endochondral bone development, a complex process that leads to the formation of the majority of skeletal elements, mesenchymal cells condense, differentiating into chondrocytes and producing the foetal growth plate. Chondrocytes progressively hypertrophy, induce angiogenesis and are then gradually replaced by bone. Epidermal Growth Factor (EGF), one of many growth factors, is the prototype of the EGF-ligand family, which comprises several proteins involved in cell proliferation, migration and survival. In bone, EGF pathway signalling finely tunes the first steps of chondrogenesis by maintaining mesenchymal cells in an undifferentiated stage, and by promoting hypertrophic cartilage replacement. Moreover, EGF signalling modulates bone homeostasis by stimulating osteoblast and osteoclast proliferation, and by regulating osteoblast differentiation under specific spatial and temporal conditions. This evidence-based narrative review describes the EGF pathway in bone metabolism and endochondral bone development. This comprehensive description may be useful in light of possible clinical applications in orthopaedic practice. A deeper knowledge of the role of EGF in bone may be useful in musculoskeletal conditions which may benefit from the modulation of this signalling pathway. The EGF pathway is involved in bone metabolism. EGF signalling is essential in the very early stages of limb development by maintaining cells in an undifferentiated stage. EGF pathway positively regulates chondrocyte proliferation, negatively modulates hypertrophy, and favours cartilage replacement by bone. EGF and EGF-like proteins finely tune the proliferation and differentiation of bone tissue cells, and they also regulate the initial phases of endochondral ossification. [ABSTRACT FROM AUTHOR]
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- 2022
- Full Text
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4. 2210PCSK9 beyond its role in cholesterol homeostasis: co-activator of platelet function
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Rossetti, L., primary, Ferri, N., additional, Marchiano, S., additional, Canciani, B., additional, Trabattoni, D., additional, Santilli, F., additional, Davi, G., additional, Tremoli, E., additional, and Camera, M., additional
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- 2017
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5. A betaPP peptide carboxyl-terminal to Abeta is neurotoxic
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MARCON, Gabriella, GIACCONE G, CANCIANI B, CAJOLA L, ROSSI G, DE GIOIA L, SALMONA M, BUGIANI O, TAGLIAVINI F., Marcon, Gabriella, Giaccone, G, Canciani, B, Cajola, L, Rossi, G, DE GIOIA, L, Salmona, M, Bugiani, O, and Tagliavini, F.
- Published
- 1999
6. Neurotoxicity of a bPP peptide other than Ab
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Marcon, G, Giaccone, G, Canciani, B, Cajola, L, Rossi, G, De Gioia, L, Salmona, M, Bugiani, O, Tagliavini, F, Marcon, G, Giaccone, G, Canciani, B, Cajola, L, Rossi, G, De Gioia, L, Salmona, M, Bugiani, O, and Tagliavini, F
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- 1996
7. bPP and Tau interaction in vitro
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Giaccone, G, Tagliavini, F, Pedrotti, B, Marcon, G, Canciani, B, De Gioia, L, Salmona, M, Bugiani, O, Giaccone, G, Tagliavini, F, Pedrotti, B, Marcon, G, Canciani, B, De Gioia, L, Salmona, M, and Bugiani, O
- Published
- 1996
8. Arrhythmia development in a young subject with right ventricular cardiomyopathy (right ventricular dysplasia)
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Bortolo Martini, Gianfranco Buja, Andrea Nava, and Canciani B
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Adult ,Male ,Right Ventricular Dysplasia ,medicine.medical_specialty ,Diagnostic methods ,business.industry ,Heart Ventricles ,Myocardium ,Cardiomyopathy ,Arrhythmias, Cardiac ,Ventriculo derecho ,medicine.disease ,Right ventricular cardiomyopathy ,Arrhythmogenic right ventricular dysplasia ,QRS complex ,Electrocardiography ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,Humans ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business ,Cardiomyopathies - Abstract
In right ventricular cardiomyopathy the relationship between the progression of structural abnormalities and arrhythmia development is not yet well known. This report describes a case in which severe ventricular arrhythmias appeared 3 years after the demonstration of right ventricular (RV) structural and dynamic abnormalities. In this interval of time structural changes were not detectable with the commonly used diagnostic methods, but endocavitary RV late fractionated QRS potentials appeared suggesting the development of an arrhythmic component of the disease.
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- 1991
9. Giant P wave in a patient with right ventricular cardiomyopathy
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Martini, B., primary, Nava, A., additional, Buja, G. F., additional, Canciani, B., additional, Bigolin, E., additional, and Dalla Volta, S., additional
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- 1990
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10. Hypertrophic cardiomyopathy: Two-dimensional echocardiographic score versus clinical and electrocardiographic findings.
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Melacini, P., Fasoli, G., Canciani, B., Buja, G., Mammola, C., and Dalla Volta, S.
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- 1989
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11. Bidirectional tachycardia. A sustained form, not related to digitalis intoxication, in an adult without apparent cardiac disease
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G. Buja, Canciani B, Bortolo Martini, and Andrea Nava
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Quinidine ,Tachycardia ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Propranolol ,Disease ,Ventricular tachycardia ,medicine.disease ,QRS complex ,Bidirectional ventricular tachycardia ,Anesthesia ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,cardiovascular diseases ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Electrocardiography ,medicine.drug - Abstract
In this paper we report the first adult case of an "idiopathic" ventricular bidirectional tachycardia (BT), in a 57 year old woman. The tachycardia, at the time of our observation, was incessant in type and had a slightly irregular frequency of about 140 bpm. BT initiated and terminated abruptly, without any temporal relationship to the preceding RR interval, or the QRS morphology. The interval between the two alternating QRS patterns often varied over a wide range of values. The BT could be interrupted only by overdrive atrial and ventricular stimulation, but promptly reappeared as pacing was discontinued. Therapy with quinidine associated with propranolol was effective on a long term trial. The vectorcardiographic analysis and the electrophysiologic investigation demonstrated a ventricular origin of the BT, localizing its site of origin to common myocardial tissue, probably near the two left hemifascicles. Our data could not elucidate the electrogenetic mechanism of this ventricular arrhythmia, because of its chaotic behavior.
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- 1988
12. Hypertrophic cardiomyopathy: Two-dimensional echocardiographic score versus clinical and electrocardiographic findings
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Giuseppe Fasoli, S. Dalla Volta, G. Buja, Paola Melacini, C. Mammola, and Canciani B
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Adult ,Male ,medicine.medical_specialty ,Myocardial ischemia ,Adolescent ,Ventricular Tachyarrhythmias ,Vectorcardiography ,Physical examination ,macromolecular substances ,Left ventricular hypertrophy ,Muscle hypertrophy ,Electrocardiography ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Aged ,Monitoring, Physiologic ,medicine.diagnostic_test ,business.industry ,Hypertrophic cardiomyopathy ,Arrhythmias, Cardiac ,General Medicine ,Cardiomyopathy, Hypertrophic ,Middle Aged ,medicine.disease ,Electrocardiographic Finding ,medicine.anatomical_structure ,Echocardiography ,Ventricle ,cardiovascular system ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
The severity and site of hypertrophy is important in determining the clinical picture and the natural history of hypertrophic cardiomyopathy (HCM). We evaluated left ventricular hypertrophy by means of two-dimensional echocardiographic score and score index, and correlated these findings with symptoms, electrovector-cardiographic data, and ventricular arrhythmias. A total of 42 patients with HCM were studied by clinical examination, ECG, VCG, M-mode and 2D echocardiography, and 24-h Holter monitoring. The extent and severity of the hypertrophic process were calculated by a score system. The left ventricle was divided into 11 segments and a hypertrophic score (HS) was given to each segment. A hypertrophy score index (HSI) was also calculated by dividing the number of hypertrophied segments by 13. No correlation was found between symptoms and HS and HSI, nor ECG-VCG abnormalities and HS and HSI. A statistically significant relationship between the severity of ventricular arrhythmias and HS and HSI was found (p less than 0.01). The mechanism responsible for ventricular tachyarrhythmias in severe and diffuse hypertrophy might reside in the high intraventricular pressures which produce or worsen areas of myocardial ischemia.
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- 1989
13. Familial occurrence of right ventricular dysplasia: A study involving nine families
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Canciani B, Paolo Stritoni, Giuseppe Fasoli, Gaetano Thiene, Andrea Nava, Bortolo Martini, Gianfranco Buja, Luciano Daliento, and Roldano Scognamiglio
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Adult ,medicine.medical_specialty ,Heart disease ,Adolescent ,Heart Ventricles ,Autopsy ,Sudden death ,Naxos disease ,Cause of Death ,medicine ,Humans ,cardiovascular diseases ,Child ,Cause of death ,Aged ,business.industry ,Fibrous dysplasia ,Angiography ,Hemodynamics ,Middle Aged ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Ventricle ,Echocardiography ,cardiovascular system ,Right Ventricular Free Wall ,Cardiology and Cardiovascular Medicine ,business ,Cardiomyopathies - Abstract
Right ventricular pathologic involvement, with autopsy evidence of fibrous and fatty infiltration of the right ventricle, was investigated in members of families in which cases of juvenile sudden death had occurred. Seventy-two subjects from nine families were studied. Sixteen died at a young age and 56 are living. Postmortem investigation in 11 cases (mean age at death 24 years) revealed massive replacement of the right ventricular free wall by fat or fibrous tissue. In the 56 living patients clinical examination included an electrocardiogram (ECG) at rest, ambulatory ECG recording, posteroanterior and lateral chest roentgenograms, M-mode and two-dimensional echocardiograms and exercise stress tests. In 14 patients, hemodynamic, angiographic and electrophysiologic studies were also carried out; right ventricular endomyocardial biopsy was performed in four. Structural and dynamic right ventricular impairment was detected in 30 living patients (mean age 25 years), and concomitant mild left ventricular abnormalities were present in 4. In eight of the nine families studied at least two members were affected. Ventricular arrhythmias (Lown grade greater than or equal to 4a) were recorded in more than half of the cases. The data reveal that right ventricular dysplasia shows a familial clustering and causes electrical instability that may place affected subjects at risk of sudden death. The mean age of these subjects suggests that the disease is manifested at a young age with a polymorphic clinical and arrhythmic profile. Finally, because this disease is a primary disorder of the ventricular myocardium, it should be included among the cardiomyopathies.
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14. Accelerated idioventricular rhythm of infundibular origin in patients with a concealed form of arrhythmogenic right ventricular dysplasia
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Bortolo Martini, Canciani B, G. Buja, Luciano Daliento, Roldano Scognamiglio, G. Thiene, Miraglia G, Andrea Nava, and Giovanni Boffa
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Adult ,Male ,Bradycardia ,medicine.medical_specialty ,Adolescent ,Accelerated idioventricular rhythm ,Heart Ventricles ,Electrocardiography ,Internal medicine ,medicine ,Humans ,Monitoring, Physiologic ,medicine.diagnostic_test ,business.industry ,Left bundle branch block ,Hemodynamics ,Arrhythmias, Cardiac ,Heart ,Middle Aged ,medicine.disease ,Arrhythmogenic right ventricular dysplasia ,medicine.anatomical_structure ,Idioventricular rhythm ,Ventricle ,Exercise Test ,Cardiology ,Female ,medicine.symptom ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business ,Right axis deviation ,Research Article - Abstract
Five apparently healthy people (aged 16-47) presented with recurrent episodes of accelerated idioventricular rhythm characterised by left bundle branch block and right axis deviation. Clinical history, physical findings, basic electrocardiogram, chest x ray, and blood tests were within normal limits in all. Holter monitoring, exercise stress test, and electrophysiological study (in three patients) showed that accelerated idioventricular rhythm was mainly bradycardia dependent, easily suppressed by effort and overdrive pacing, and originated from the outflow tract of the right ventricle. The mechanism could be enhanced automaticity. Data from cross sectional echocardiography (in all patients) and from haemodynamic evaluation (in three) identified structural or wall motion abnormalities of the right ventricle or both without appreciable dilatation of the ventricle. Biopsy specimens of the right ventricular endomyocardium showed fibrosis in one patient, fibrosis and fatty infiltration in the second, and pronounced fatty infiltration in the third. These results show that some patients with accelerated idioventricular rhythm have right ventricular abnormalities that are typical of the localised and concealed forms of arrhythmogenic right ventricular dysplasia.
15. Giant P wave in a patient with right ventricular cardiomyopathy
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Bortolo Martini, E. Bigolin, Andrea Nava, G. Buja, S. Dalla Volta, and Canciani B
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Adult ,Heart Defects, Congenital ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Heart Ventricles ,Cardiomyopathy ,Regurgitation (circulation) ,Right ventricular cardiomyopathy ,Electrocardiography ,QRS complex ,Heart Conduction System ,T wave ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,medicine.diagnostic_test ,business.industry ,P wave ,General Medicine ,Cardiomyopathy, Hypertrophic ,medicine.disease ,Atrial Flutter ,Echocardiography ,cardiovascular system ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Atrial flutter ,Follow-Up Studies - Abstract
A P wave of 7.5 mm in lead I and 12.5 in V1 was detected in a 28-year-old man, with a progressive cardiomegaly since the age of 14 years. At last admission he had minor symptoms, and a systolic murmur consistent with tricuspid regurgitation. The electrocardiogram showed an extremely tall P wave and a QRS of a very low amplitude; T waves were inverted on the precordial leads. These ECG features, and subsequent investigations, were consistent with right ventricular cardiomyopathy with massive tricuspid regurgitation, and right atrial abnormality.
16. Right bundle branch block, persistent ST segment elevation and sudden cardiac death
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Bortolo Martini, Andrea Nava, Gaetano Thiene, and Canciani B
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Elevation ,Right bundle branch block ,medicine.disease ,Sudden cardiac death ,Internal medicine ,medicine ,Cardiology ,ST segment ,Cardiology and Cardiovascular Medicine ,business ,Electrocardiography - Full Text
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17. High-throughput screening for modulators of ACVR1 transcription: discovery of potential therapeutics for fibrodysplasia ossificans progressiva
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Serena Cappato, Laura Tonachini, Francesca Giacopelli, Mario Tirone, Luis J. V. Galietta, Martina Sormani, Anna Giovenzana, Antonello E. Spinelli, Barbara Canciani, Silvia Brunelli, Roberto Ravazzolo, Renata Bocciardi, Cappato, S, Tonachini, L, Giacopelli, F, Tirone, M, Galietta, L, Sormani, M, Giovenzana, A, Spinelli, A, Canciani, B, Brunelli, S, Ravazzolo, R, Bocciardi, R, Cappato, Serena, Tonachini, Laura, Giacopelli, Francesca, Tirone, Mario, Galietta, Luis J. V., Sormani, Martina, Giovenzana, Anna, Spinelli, Antonello E., Canciani, Barbara, Brunelli, Silvia, Ravazzolo, Roberto, and Bocciardi, Renata
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High-Throughput Screening Assay ,Myositis Ossifican ,Transcription, Genetic ,Neuroscience (miscellaneous) ,lcsh:Medicine ,Reproducibility of Result ,Medicine (miscellaneous) ,BMP signaling pathway ,Smad Proteins ,ACVR1 ,Fibrodysplasia Ossificans Progressiva ,Cell Line ,Mice ,Transcriptional regulation ,Immunology and Microbiology (miscellaneous) ,Osteogenesis ,lcsh:Pathology ,Animals ,FOP ,Biochemistry, Genetics and Molecular Biology (all) ,Osteoblasts ,Animal ,Smad Protein ,Bone Morphogenetic Protein ,Osteoblast ,Osteogenesi ,Ossification, Heterotopic ,lcsh:R ,Drug repositioning ,High-throughput screening ,BIO/13 - BIOLOGIA APPLICATA ,Reproducibility of Results ,Correction ,Cell Differentiation ,Biomarker ,Dipyridamole ,High-Throughput Screening Assays ,Disease Models, Animal ,Myositis Ossificans ,Bone Morphogenetic Proteins ,Chondrogenesi ,Calcium ,Activin Receptors, Type I ,Chondrogenesis ,Biomarkers ,lcsh:RB1-214 ,Signal Transduction - Abstract
The ACVR1 gene encodes a type I receptor of bone morphogenetic proteins (BMPs). Activating mutations in ACVR1 are responsible for fibrodysplasia ossificans progressiva (FOP), a rare disease characterized by congenital toe malformation and progressive heterotopic endochondral ossification leading to severe and cumulative disability. Until now, no therapy has been available to prevent soft-tissue swelling (flare-ups) that trigger the ossification process. With the aim of finding a new therapeutic strategy for FOP, we developed a high-throughput screening (HTS) assay to identify inhibitors of ACVR1 gene expression among drugs already approved for the therapy of other diseases. The screening, based on an ACVR1 promoter assay, was followed by an in vitro and in vivo test to validate and characterize candidate molecules. Among compounds that modulate the ACVR1 promoter activity, we selected the one showing the highest inhibitory effect, dipyridamole, a drug that is currently used as a platelet anti-aggregant. The inhibitory effect was detectable on ACVR1 gene expression, on the whole Smad-dependent BMP signaling pathway, and on chondrogenic and osteogenic differentiation processes by in vitro cellular assays. Moreover, dipyridamole reduced the process of heterotopic bone formation in vivo. Our drug repositioning strategy has led to the identification of dipyridamole as a possible therapeutic tool for the treatment of FOP. Furthermore, our study has also defined a pipeline of assays that will be useful for the evaluation of other pharmacological inhibitors of heterotopic ossification.
- Published
- 2015
18. Bone turnover in wild type and pleiotrophin-transgenic mice housed for three months in the international space station (ISS)
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Francesco Brun, Delfina Costa, Alessandra Ruggiu, Yu-yi Liu, Adrian Manescu, Franco Rustichelli, Sara Tavella, Roberta Tasso, Ranieri Cancedda, Federica Piccardi, Giuliana Tromba, Alessandra Giuliani, Katia Marozzi, Barbara Canciani, Michele Cilli, Tavella, S., Ruggiu, A., Giuliani, A., Brun, Francesco, Canciani, B., Manescu, A., Marozzi, K., Cilli, M., Costa, D., Liu, Y., Piccardi, F., Tasso, R., Tromba, G., Rustichelli, F., and Cancedda, R.
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Pathology ,bone turnover ,Bone density ,Astronomical Sciences ,Veterinary Anatomy and Physiology ,animal cell ,Pleiotrophin ,weight bearing ,Bone remodeling ,law.invention ,Weight-Bearing ,Mice ,law ,Molecular Cell Biology ,osteoporosi ,animal experiment ,animal tissue ,article ,controlled study ,gene expression ,male ,micro-computed tomography ,microgravity ,mouse ,nonhuman ,ossification ,osteocyte ,osteolysis ,osteoporosis ,PTN transgene ,space ,space flight ,thickness ,transgene ,transgenic mouse ,wild type ,Multidisciplinary ,Physics ,Electromagnetic Radiation ,Osteoblast ,Animal Models ,Space Exploration ,Resorption ,medicine.anatomical_structure ,Osteocyte ,osteolysi ,Medicine ,thickne ,Cytokines ,Bone Remodeling ,Genetic Engineering ,Research Article ,Biotechnology ,medicine.medical_specialty ,Science ,Mice, Transgenic ,Spaceflight ,Osteocytes ,Bone resorption ,Bone and Bones ,Model Organisms ,Internal medicine ,medicine ,Genetics ,Animals ,Spiro Compounds ,Biology ,DNA Primers ,Weightlessness ,X-Ray Microtomography ,Astrobiology ,Mice, Inbred C57BL ,Endocrinology ,Veterinary Science ,Carrier Proteins - Abstract
Bone is a complex dynamic tissue undergoing a continuous remodeling process. Gravity is a physical force playing a role in the remodeling and contributing to the maintenance of bone integrity. This article reports an investigation on the alterations of the bone microarchitecture that occurred in wild type (Wt) and pleiotrophin-transgenic (PTN-Tg) mice exposed to a near-zero gravity on the International Space Station (ISS) during the Mice Drawer System (MDS) mission, to date, the longest mice permanence (91 days) in space. The transgenic mouse strain over-expressing pleiotrophin (PTN) in bone was selected because of the PTN positive effects on bone turnover. Wt and PTN-Tg control animals were maintained on Earth either in a MDS payload or in a standard vivarium cage. This study revealed a bone loss during spaceflight in the weight-bearing bones of both strains. For both Tg and Wt a decrease of the trabecular number as well as an increase of the mean trabecular separation was observed after flight, whereas trabecular thickness did not show any significant change. Non weight-bearing bones were not affected. The PTN-Tg mice exposed to normal gravity presented a poorer trabecular organization than Wt mice, but interestingly, the expression of the PTN transgene during the flight resulted in some protection against microgravity's negative effects. Moreover, osteocytes of the Wt mice, but not of Tg mice, acquired a round shape, thus showing for the first time osteocyte space-related morphological alterations in vivo. The analysis of specific bone formation and resorption marker expression suggested that the microgravity-induced bone loss was due to both an increased bone resorption and a decreased bone deposition. Apparently, the PTN transgene protection was the result of a higher osteoblast activity in the flight mice.
- Published
- 2012
19. Creutzfeldt-Jakob disease: Carnoy's fixative improves the immunohistochemistry of the proteinase K-resistant prion protein
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Gianfranco Puoti, Giacomina Rossi, Orso Bugiani, B. Canciani, Paolo Fociani, Donato Goffredo, Giorgio Giaccone, Selina Iussich, Fabrizio Tagliavini, Giaccone, G, Canciani, B, Puoti, Gianfranco, Rossi, G, Goffredo, D, Iussich, S, Fociani, P, Tagliavini, F, and Bugiani, O.
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Adult ,Male ,Antigenicity ,Prions ,animal diseases ,Biology ,Creutzfeldt-Jakob Syndrome ,Pathology and Forensic Medicine ,PRNP ,Immunolabeling ,Fixatives ,Western blot ,medicine ,Humans ,Fixative ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,General Neuroscience ,Brain ,Middle Aged ,Proteinase K ,Molecular biology ,Immunohistochemistry ,nervous system diseases ,Biochemistry ,biology.protein ,Female ,Neurology (clinical) ,Endopeptidase K ,Immunostaining ,Research Article - Abstract
The neuropathological diagnosis of Creutzfeldt‐Jakob disease relies on the immunohistochemical demonstration of the proteinase‐K resistant form of the prion protein (PrP(res)) in the brain tissue. The antigenicity of PrP(res) is strongly reduced by the formalin solution widely used to fix the tissue, thus the PrP(res) immunoreactivity is inconsistently detectable in formalin‐fixed tissue. A better PrP(res) immunostaining can be obtained by using Carnoy's fixing solution, which is composed of ethanol, chloroform and acetic acid (6:3:1). PrP(res) can easily be extracted from Carnoy's‐fixed, paraplast‐embedded tissue. Accordingly, Carnoy's‐fixed tissue can prior to immunolabeling be subjected to proteinase K and guanidine thio‐cyanate, which respectively eliminate the normal cellular form of prion protein and promote protein denaturation. In comparison with the best protocols for formalin‐fixed tissue (i.e. ‐ hydrolytic autoclaving or autoclaving in distilled water followed by formic acid and guanidine thiocyanate), PrP(res) immunostaining carried out on sections cut from Carnoy's‐fixed, paraplast‐embedded tissue blocks and subjected to proteinase K and guanidine thiocyanate, proved more successful to detect and map both diffuse and focal PrP(res) immunoreactivity, and to correlate the immunoreactivity pattern with MV polymorphism at PRNP codon 129 and PrP(res) banding and glycosyla‐tion pattern revealed by Western blot.
- Published
- 2000
20. In Vitro and In Vivo Biocompatibility Assessment of a Thermosensitive Injectable Chitosan-Based Hydrogel for Musculoskeletal Tissue Engineering.
- Author
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Canciani B, Semeraro F, Herrera Millar VR, Gervaso F, Polini A, Stanzione A, Peretti GM, Di Giancamillo A, and Mangiavini L
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- Mice, Humans, Animals, Swine, Tissue Engineering, Mice, Nude, Cell Differentiation, Tissue Scaffolds, Hydrogels, Chitosan
- Abstract
Musculoskeletal impairments, especially cartilage and meniscus lesions, are some of the major contributors to disabilities. Thus, novel tissue engineering strategies are being developed to overcome these issues. In this study, the aim was to investigate the biocompatibility, in vitro and in vivo, of a thermosensitive, injectable chitosan-based hydrogel loaded with three different primary mesenchymal stromal cells. The cell types were human adipose-derived mesenchymal stromal cells (hASCs), human bone marrow stem cells (hBMSCs), and neonatal porcine infrapatellar fat-derived cells (IFPCs). For the in vitro study, the cells were encapsulated in sol-phase hydrogel, and then, analyzed via live/dead assay at 1, 4, 7, and 14 days to compare their capacity to survive in the hydrogel. To assess biocompatibility in vivo, cellularized scaffolds were subcutaneously implanted in the dorsal pouches of nude mice and analyzed at 4 and 12 weeks. Our data showed that all the different cell types survived (the live cell percentages were between 60 and 80 at all time points in vitro) and proliferated in the hydrogel (from very few at 4 weeks to up to 30% at 12 weeks in vivo); moreover, the cell-laden hydrogels did not trigger an immune response in vivo. Hence, our hydrogel formulation showed a favorable profile in terms of safety and biocompatibility, and it may be applied in tissue engineering strategies for cartilage and meniscus repair.
- Published
- 2023
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21. Endostatin in 3D Fibrin Hydrogel Scaffolds Promotes Chondrogenic Differentiation in Swine Neonatal Meniscal Cells.
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Herrera Millar VR, Canciani B, Mangiavini L, Filipe JFS, Aidos L, Pallaoro M, Peretti GM, Pocar P, Modina SC, and Di Giancamillo A
- Abstract
The success of cell-based approaches for the treatment of cartilage or fibro-cartilaginous tissue defects requires an optimal cell source with chondrogenic differentiation ability that maintains its differentiated properties and stability following implantation. For this purpose, the aim of this study was to evaluate the use of endostatin (COL18A1), an anti-angiogenic factor, which is physiologically involved in cell differentiation during meniscus development. Swine neonatal meniscal cells not yet subjected to mechanical stimuli were extracted, cultured in fibrin hydrogel scaffolds, and treated at two different time points (T1 = 9 days and T2 = 21 days) with different concentrations of COL18A1 (10 ng/mL; 100 ng/mL; 200 ng/mL). At the end of the treatments, the scaffolds were examined through biochemical, molecular, and histochemical analyses. The results showed that the higher concentration of COL18A1 promotes a fibro-chondrogenic phenotype and improves cellularity index (DNA content, p < 0.001) and cell efficiency (GAGs/DNA ratio, p < 0.01) after 21 days. These data are supported by the molecular analysis of collagen type I (COL1A1, a marker of fibrous-like tissue, p < 0.001), collagen type II (COL2A1, a marker of cartilaginous-like tissue, p < 0.001) and SRY-Box Transcription Factor 9 (SOX9, an early marker of chondrogenicity, p < 0.001), as well as by histological analysis (Safranin-O staining), laying the foundations for future studies evaluating the involvement of 3D endostatin hydrogel scaffolds in the differentiation of avascular tissues.
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- 2022
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22. Human Sarcopenic Myoblasts Can Be Rescued by Pharmacological Reactivation of HIF-1α.
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Cirillo F, Mangiavini L, La Rocca P, Piccoli M, Ghiroldi A, Rota P, Tarantino A, Canciani B, Coviello S, Messina C, Ciconte G, Pappone C, Peretti GM, and Anastasia L
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- Aged, Humans, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Muscle, Skeletal metabolism, Myoblasts, Stem Cells, Sarcopenia metabolism
- Abstract
Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. It is associated with decreased tissue vascularization and muscle atrophy. In this work, we investigated the role of the hypoxia inducible factor HIF-1α in sarcopenia. To this end, we obtained skeletal muscle biopsies from elderly sarcopenic patients and compared them with those from young individuals. We found a decrease in the expression of HIF-1α and its target genes in sarcopenia, as well as of PAX7 , the major stem cell marker of satellite cells, whereas the atrophy marker MURF1 was increased. We also isolated satellite cells from muscle biopsies and cultured them in vitro. We found that a pharmacological activation of HIF-1α and its target genes caused a reduction in skeletal muscle atrophy and activation of PAX7 gene expression. In conclusion, in this work we found that HIF-1α plays a role in sarcopenia and is involved in satellite cell homeostasis. These results support further studies to test whether pharmacological reactivation of HIF-1α could prevent and counteract sarcopenia.
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- 2022
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23. Testing Hypoxia in Pig Meniscal Culture: Biological Role of the Vascular-Related Factors in the Differentiation and Viability of Neonatal Meniscus.
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Canciani B, Herrera Millar VR, Pallaoro M, Aidos L, Cirillo F, Anastasia L, Peretti GM, Modina SC, Mangiavini L, and Di Giancamillo A
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- Animals, Animals, Newborn, Biomarkers metabolism, Caspase 3 genetics, Caspase 3 metabolism, Cell Differentiation drug effects, Chondrocytes cytology, Chondrocytes metabolism, Collagen Type I genetics, Collagen Type I metabolism, Collagen Type II genetics, Collagen Type II metabolism, Endostatins genetics, Endostatins metabolism, Fibroblasts cytology, Fibroblasts metabolism, Gene Expression, Hypoxia genetics, Menisci, Tibial cytology, Menisci, Tibial metabolism, Platelet Endothelial Cell Adhesion Molecule-1 genetics, Platelet Endothelial Cell Adhesion Molecule-1 metabolism, Proliferating Cell Nuclear Antigen genetics, Proliferating Cell Nuclear Antigen metabolism, SOX9 Transcription Factor genetics, SOX9 Transcription Factor metabolism, Swine, Tissue Culture Techniques, Chondrocytes drug effects, Fibroblasts drug effects, Hypoxia metabolism, Menisci, Tibial drug effects, Oxygen pharmacology
- Abstract
Menisci play an essential role in shock absorption, joint stability, load resistance and its transmission thanks to their conformation. Adult menisci can be divided in three zones based on the vascularization: an avascular inner zone with no blood supply, a fully vascularized outer zone, and an intermediate zone. This organization, in addition to the incomplete knowledge about meniscal biology, composition, and gene expression, makes meniscal regeneration still one of the major challenges both in orthopedics and in tissue engineering. To overcome this issue, we aimed to investigate the role of hypoxia in the differentiation of the three anatomical areas of newborn piglet menisci (anterior horn (A), central body (C), and posterior horn (P)) and its effects on vascular factors. After sample collection, menisci were divided in A, C, P, and they were cultured in vitro under hypoxic (1% O
2 ) and normoxic (21% O2 ) conditions at four different experimental time points (T0 = day of explant; T7 = day 7; T10 = day 10; T14 = day 14); samples were then evaluated through immune, histological, and molecular analyses, cell morpho-functional characteristics; with particular focus on matrix composition and expression of vascular factors. It was observed that hypoxia retained the initial phenotype of cells and induced extracellular matrix production resembling a mature tissue. Hypoxia also modulated the expression of angiogenic factors, especially in the early phase of the study. Thus, we observed that hypoxia contributes to the fibro-chondrogenic differentiation with the involvement of angiogenic factors, especially in the posterior horn, which corresponds to the predominant weight-bearing portion.- Published
- 2021
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24. Hypoxia as a Stimulus for the Maturation of Meniscal Cells: Highway to Novel Tissue Engineering Strategies?
- Author
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Herrera Millar VR, Mangiavini L, Polito U, Canciani B, Nguyen VT, Cirillo F, Anastasia L, Peretti GM, Modina SC, and Di Giancamillo A
- Subjects
- Animals, Biomarkers, Cells, Cultured, Chondrocytes metabolism, Gene Expression, Glycosaminoglycans metabolism, Hypoxia genetics, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Immunohistochemistry, Swine, Tissue Engineering methods, Cell Differentiation, Hypoxia metabolism, Meniscus cytology, Meniscus metabolism
- Abstract
The meniscus possesses low self-healing properties. A perfect regenerative technique for this tissue has not yet been developed. This work aims to evaluate the role of hypoxia in meniscal development in vitro. Menisci from neonatal pigs (day 0) were harvested and cultured under two different atmospheric conditions: hypoxia (1% O
2 ) and normoxia (21% O2 ) for up to 14 days. Samples were analysed at 0, 7 and 14 days by histochemical (Safranin-O staining), immunofluorescence and RT-PCR (in both methods for SOX-9, HIF-1α, collagen I and II), and biochemical (DNA, GAGs, DNA/GAGs ratio) techniques to record any possible differences in the maturation of meniscal cells. Safranin-O staining showed increments in matrix deposition and round-shape "fibro-chondrocytic" cells in hypoxia-cultured menisci compared with controls under normal atmospheric conditions. The same maturation shifting was observed by immunofluorescence and RT-PCR analysis: SOX-9 and collagen II increased from day zero up to 14 days under a hypoxic environment. An increment of DNA/GAGs ratio typical of mature meniscal tissue (characterized by fewer cells and more GAGs) was observed by biochemical analysis. This study shows that hypoxia can be considered as a booster to achieve meniscal cell maturation, and opens new opportunities in the field of meniscus tissue engineering.- Published
- 2021
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- View/download PDF
25. Effect of Chemically Induced Hypoxia on Osteogenic and Angiogenic Differentiation of Bone Marrow Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells in Direct Coculture.
- Author
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Nguyen VT, Canciani B, Cirillo F, Anastasia L, Peretti GM, and Mangiavini L
- Subjects
- Aged, Aged, 80 and over, Biomarkers metabolism, Cell Hypoxia, Cell Proliferation, Coculture Techniques, Human Umbilical Vein Endothelial Cells metabolism, Humans, Mesenchymal Stem Cells metabolism, Middle Aged, von Willebrand Factor metabolism, Cell Differentiation, Human Umbilical Vein Endothelial Cells cytology, Mesenchymal Stem Cells cytology, Neovascularization, Physiologic, Osteogenesis
- Abstract
Bone is an active tissue where bone mineralization and resorption occur simultaneously. In the case of fracture, there are numerous factors required to facilitate bone healing including precursor cells and blood vessels. To evaluate the interaction between bone marrow-derived mesenchymal stem cells (BMSC)-the precursor cells able to differentiate into bone-forming cells and human umbilical vein endothelial cells (HUVEC)-a cell source widely used for the study of blood vessels. We performed direct coculture of BMSC and HUVEC in normoxia and chemically induced hypoxia using Cobalt(II) chloride and Dimethyloxaloylglycine and in the condition where oxygen level was maintained at 1% as well. Cell proliferation was analyzed by crystal violet staining. Osteogenesis was examined by Alizarin Red and Collagen type I staining. Expression of angiogenic factor-vascular endothelial growth factor (VEGF) and endothelial marker-von Willebrand factor (VWF) were demonstrated by immunohistochemistry and enzyme-linked immunosorbent assay. The quantitative polymerase chain reaction was also used to evaluate gene expression. The results showed that coculture in normoxia could retain both osteogenic differentiation and endothelial markers while hypoxic condition limits cell proliferation and osteogenesis but favors the angiogenic function even after 1 of day treatment., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
- Published
- 2020
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26. CFSE: A New Method for Identifying Human Limbal Stem Cells and Following Their Migration in Human Cornea.
- Author
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Bonzano C, Canciani B, Olivari S, Papadia M, Bagnis A, Cutolo CA, Bonzano E, Pagani P, Cancedda R, and Traverso CE
- Subjects
- Cell Culture Techniques methods, Cell Proliferation physiology, Cornea metabolism, Epithelium, Corneal metabolism, Humans, Stem Cells metabolism, Cell Movement physiology, Cornea physiology, Epithelium, Corneal physiology, Fluoresceins metabolism, Stem Cells physiology, Succinimides metabolism
- Abstract
Aim: To develop a method capable of identifying human corneal limbal stem cells (LSCs) and follow their proliferation and migration in the epithelium., Materials and Methods: Ten fresh matched pairs of cadaveric normal human corneas were obtained from donors. Carboxyfluorescein diacetate succinimidyl ester (CFSE) was used to target LSCs. The distribution of CFSE-positive cell clusters was analyzed by fluorescence microscopy by counterstaining with 4',6-diamidino-2-phenylindole (DAPI). Fluorescence was digitally recorded for seven days, and the rate of cell movement was determined., Results: CFSE-labeled cells were tracked in corneas. Analysis of time sequences revealed that they moved centripetally. Daily average CFSE-labeled LSC movement was 0.073±0.01 cm (±SD)., Conclusion: CFSE allowed us to identify LSCs and to track their centripetal migration from the limbal basal layer to the anterior ocular surface. This experimental system appears to be a valuable tool for further studies on corneal epithelial cell migration and proliferation., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2019
- Full Text
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27. High-Resolution X-Ray Tomography: A 3D Exploration Into the Skeletal Architecture in Mouse Models Submitted to Microgravity Constraints.
- Author
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Giuliani A, Mazzoni S, Ruggiu A, Canciani B, Cancedda R, and Tavella S
- Abstract
Bone remodeling process consists in a slow building phase and in faster resorption with the objective to maintain a functional skeleton locomotion to counteract the Earth gravity. Thus, during spaceflights, the skeleton does not act against gravity, with a rapid decrease of bone mass and density, favoring bone fracture. Several studies approached the problem by imaging the bone architecture and density of cosmonauts returned by the different spaceflights. However, the weaknesses of the previously reported studies was two-fold: on the one hand the research suffered the small statistical sample size of almost all human spaceflight studies, on the other the results were not fully reliable, mainly due to the fact that the observed bone structures were small compared with the spatial resolution of the available imaging devices. The recent advances in high-resolution X-ray tomography have stimulated the study of weight-bearing skeletal sites by novel approaches, mainly based on the use of the mouse and its various strains as an animal model, and sometimes taking advantage of the synchrotron radiation support to approach studies of 3D bone architecture and mineralization degree mapping at different hierarchical levels. Here we report the first, to our knowledge, systematic review of the recent advances in studying the skeletal bone architecture by high-resolution X-ray tomography after submission of mice models to microgravity constrains.
- Published
- 2018
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28. PCSK9 as a Positive Modulator of Platelet Activation.
- Author
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Camera M, Rossetti L, Barbieri SS, Zanotti I, Canciani B, Trabattoni D, Ruscica M, Tremoli E, and Ferri N
- Subjects
- Adult, Animals, Biomarkers blood, Female, Humans, Male, Mice, Mice, Transgenic, Platelet Activation physiology, Platelet-Rich Plasma metabolism, Proprotein Convertase 9 blood
- Published
- 2018
- Full Text
- View/download PDF
29. Correction: High-throughput screening for modulators of ACVR1 transcription: discovery of potential therapeutics for fibrodysplasia ossificans progressiva.
- Author
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Cappato S, Tonachini L, Giacopelli F, Tirone M, Galietta LJ, Sormani M, Giovenzana A, Spinelli AE, Canciani B, Brunelli S, Ravazzolo R, and Bocciardi R
- Published
- 2016
- Full Text
- View/download PDF
30. High-throughput screening for modulators of ACVR1 transcription: discovery of potential therapeutics for fibrodysplasia ossificans progressiva.
- Author
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Cappato S, Tonachini L, Giacopelli F, Tirone M, Galietta LJ, Sormani M, Giovenzana A, Spinelli AE, Canciani B, Brunelli S, Ravazzolo R, and Bocciardi R
- Subjects
- Animals, Biomarkers metabolism, Bone Morphogenetic Proteins metabolism, Calcium metabolism, Cell Differentiation drug effects, Cell Line, Chondrogenesis drug effects, Dipyridamole pharmacology, Dipyridamole therapeutic use, Disease Models, Animal, Mice, Myositis Ossificans metabolism, Myositis Ossificans pathology, Ossification, Heterotopic diagnostic imaging, Ossification, Heterotopic pathology, Osteoblasts cytology, Osteoblasts drug effects, Osteoblasts metabolism, Osteogenesis drug effects, Reproducibility of Results, Signal Transduction drug effects, Smad Proteins metabolism, Activin Receptors, Type I genetics, High-Throughput Screening Assays methods, Myositis Ossificans drug therapy, Transcription, Genetic drug effects
- Abstract
The ACVR1 gene encodes a type I receptor of bone morphogenetic proteins (BMPs). Activating mutations in ACVR1 are responsible for fibrodysplasia ossificans progressiva (FOP), a rare disease characterized by congenital toe malformation and progressive heterotopic endochondral ossification leading to severe and cumulative disability. Until now, no therapy has been available to prevent soft-tissue swelling (flare-ups) that trigger the ossification process. With the aim of finding a new therapeutic strategy for FOP, we developed a high-throughput screening (HTS) assay to identify inhibitors of ACVR1 gene expression among drugs already approved for the therapy of other diseases. The screening, based on an ACVR1 promoter assay, was followed by an in vitro and in vivo test to validate and characterize candidate molecules. Among compounds that modulate the ACVR1 promoter activity, we selected the one showing the highest inhibitory effect, dipyridamole, a drug that is currently used as a platelet anti-aggregant. The inhibitory effect was detectable on ACVR1 gene expression, on the whole Smad-dependent BMP signaling pathway, and on chondrogenic and osteogenic differentiation processes by in vitro cellular assays. Moreover, dipyridamole reduced the process of heterotopic bone formation in vivo Our drug repositioning strategy has led to the identification of dipyridamole as a possible therapeutic tool for the treatment of FOP. Furthermore, our study has also defined a pipeline of assays that will be useful for the evaluation of other pharmacological inhibitors of heterotopic ossification., (© 2016. Published by The Company of Biologists Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
31. Evaluation of the effect of a gamma irradiated DBM-pluronic F127 composite on bone regeneration in Wistar rat.
- Author
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Al Kayal T, Panetta D, Canciani B, Losi P, Tripodi M, Burchielli S, Ottoni P, Salvadori PA, and Soldani G
- Subjects
- Animals, Biomarkers metabolism, Bone Density, Bone Matrix chemistry, Bone Matrix physiology, Bone Morphogenetic Protein 2 genetics, Bone Morphogenetic Protein 2 metabolism, Bone Morphogenetic Protein 7 genetics, Bone Morphogenetic Protein 7 metabolism, Femur injuries, Femur surgery, Gamma Rays, Gene Expression, Humans, Male, Rats, Rats, Wistar, X-Ray Microtomography, Biocompatible Materials chemistry, Bone Matrix radiation effects, Bone Regeneration physiology, Poloxamer chemistry
- Abstract
Demineralized bone matrix (DBM) is widely used for bone regeneration. Since DBM is prepared in powder form its handling properties are not optimal and limit the clinical use of this material. Various synthetic and biological carriers have been used to enhance the DBM handling. In this study we evaluated the effect of gamma irradiation on the physical-chemical properties of Pluronic and on bone morphogenetic proteins (BMPs) amount in DBM samples. In vivo studies were carried out to investigate the effect on bone regeneration of a gamma irradiated DBM-Pluronic F127 (DBM-PF127) composite implanted in the femur of rats. Gamma irradiation effects (25 kGy) on physical-chemical properties of Pluronic F127 were investigated by rheological and infrared analysis. The BMP-2/BMP-7 amount after DBM irradiation was evaluated by ELISA. Bone regeneration capacity of DBM-PF127 containing 40% (w/w) of DBM was investigated in transcortical holes created in the femoral diaphysis of Wistar rat. Bone porosity, repaired bone volume and tissue organization were evaluated at 15, 30 and 90 days by Micro-CT and histological analysis. The results showed that gamma irradiation did not induce significant modification on physical-chemical properties of Pluronic, while a decrease in BMP-2/BMP-7 amount was evidenced in sterilized DBM. Micro-CT and histological evaluation at day 15 post-implantation revealed an interconnected trabeculae network in medullar cavity and cellular infiltration and vascularization of DBM-PF127 residue. In contrast a large rate of not connected trabeculae was observed in Pluronic filled and unfilled defects. At 30 and 90 days the DBM-PF127 samples shown comparable results in term of density and thickness of the new formed tissue respect to unfilled defect. In conclusion a gamma irradiated DBM-PF127 composite, although it may have undergone a significant decrease in the concentration of BMPs, was able to maintains bone regeneration capability.
- Published
- 2015
- Full Text
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32. Bone turnover in wild type and pleiotrophin-transgenic mice housed for three months in the International Space Station (ISS).
- Author
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Tavella S, Ruggiu A, Giuliani A, Brun F, Canciani B, Manescu A, Marozzi K, Cilli M, Costa D, Liu Y, Piccardi F, Tasso R, Tromba G, Rustichelli F, and Cancedda R
- Subjects
- Animals, Bone and Bones cytology, Bone and Bones diagnostic imaging, Bone and Bones physiology, DNA Primers genetics, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Osteocytes cytology, Osteocytes physiology, Spiro Compounds, Weight-Bearing physiology, X-Ray Microtomography, Bone Remodeling genetics, Bone Remodeling physiology, Carrier Proteins genetics, Carrier Proteins physiology, Cytokines genetics, Cytokines physiology, Space Flight, Weightlessness adverse effects
- Abstract
Bone is a complex dynamic tissue undergoing a continuous remodeling process. Gravity is a physical force playing a role in the remodeling and contributing to the maintenance of bone integrity. This article reports an investigation on the alterations of the bone microarchitecture that occurred in wild type (Wt) and pleiotrophin-transgenic (PTN-Tg) mice exposed to a near-zero gravity on the International Space Station (ISS) during the Mice Drawer System (MDS) mission, to date, the longest mice permanence (91 days) in space. The transgenic mouse strain over-expressing pleiotrophin (PTN) in bone was selected because of the PTN positive effects on bone turnover. Wt and PTN-Tg control animals were maintained on Earth either in a MDS payload or in a standard vivarium cage. This study revealed a bone loss during spaceflight in the weight-bearing bones of both strains. For both Tg and Wt a decrease of the trabecular number as well as an increase of the mean trabecular separation was observed after flight, whereas trabecular thickness did not show any significant change. Non weight-bearing bones were not affected. The PTN-Tg mice exposed to normal gravity presented a poorer trabecular organization than Wt mice, but interestingly, the expression of the PTN transgene during the flight resulted in some protection against microgravity's negative effects. Moreover, osteocytes of the Wt mice, but not of Tg mice, acquired a round shape, thus showing for the first time osteocyte space-related morphological alterations in vivo. The analysis of specific bone formation and resorption marker expression suggested that the microgravity-induced bone loss was due to both an increased bone resorption and a decreased bone deposition. Apparently, the PTN transgene protection was the result of a higher osteoblast activity in the flight mice.
- Published
- 2012
- Full Text
- View/download PDF
33. Sprouty proteins inhibit receptor-mediated activation of phosphatidylinositol-specific phospholipase C.
- Author
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Akbulut S, Reddi AL, Aggarwal P, Ambardekar C, Canciani B, Kim MK, Hix L, Vilimas T, Mason J, Basson MA, Lovatt M, Powell J, Collins S, Quatela S, Phillips M, and Licht JD
- Subjects
- Adaptor Proteins, Signal Transducing, Animals, Antigens, CD metabolism, Antigens, Differentiation, T-Lymphocyte metabolism, Biomarkers metabolism, Calcium metabolism, Diglycerides metabolism, Enzyme Activation, Immunoprecipitation, Inositol 1,4,5-Trisphosphate metabolism, Intracellular Signaling Peptides and Proteins, Intracellular Space metabolism, Lectins, C-Type metabolism, Mice, Mitogen-Activated Protein Kinases metabolism, NIH 3T3 Cells, Protein Binding, Protein Serine-Threonine Kinases, T-Lymphocytes metabolism, Transcription, Genetic, ras Proteins metabolism, Membrane Proteins metabolism, Phospholipase C gamma metabolism, Phosphoproteins metabolism, Receptors, Antigen, T-Cell metabolism
- Abstract
Sprouty (Spry) proteins are negative regulators of receptor tyrosine kinase signaling; however, their exact mechanism of action remains incompletely understood. We identified phosphatidylinositol-specific phospholipase C (PLC)-γ as a partner of the Spry1 and Spry2 proteins. Spry-PLCγ interaction was dependent on the Src homology 2 domain of PLCγ and a conserved N-terminal tyrosine residue in Spry1 and Spry2. Overexpression of Spry1 and Spry2 was associated with decreased PLCγ phosphorylation and decreased PLCγ activity as measured by production of inositol (1,4,5)-triphosphate (IP(3)) and diacylglycerol, whereas cells deficient for Spry1 or Spry1, -2, and -4 showed increased production of IP(3) at baseline and further increased in response to growth factor signals. Overexpression of Spry 1 or Spry2 or small-interfering RNA-mediated knockdown of PLCγ1 or PLCγ2 abrogated the activity of a calcium-dependent reporter gene, suggesting that Spry inhibited calcium-mediated signaling downstream of PLCγ. Furthermore, Spry overexpression in T-cells, which are highly dependent on PLCγ activity and calcium signaling, blocked T-cell receptor-mediated calcium release. Accordingly, cultured T-cells from Spry1 gene knockout mice showed increased proliferation in response to T-cell receptor stimulation. These data highlight an important action of Spry, which may allow these proteins to influence signaling through multiple receptors.
- Published
- 2010
- Full Text
- View/download PDF
34. Dopamine D1-receptors modulate lateral inhibition between principal cells of the nucleus accumbens.
- Author
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Taverna S, Canciani B, and Pennartz CM
- Subjects
- 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine pharmacology, Animals, Benzazepines pharmacology, Dopamine pharmacology, Dose-Response Relationship, Drug, Drug Interactions, Lysine metabolism, Male, Neural Inhibition drug effects, Neurons classification, Neurons drug effects, Rats, Rats, Wistar, Receptors, Dopamine D1 agonists, Receptors, Dopamine D1 antagonists & inhibitors, Synaptic Transmission drug effects, Synaptic Transmission physiology, Functional Laterality physiology, Lysine analogs & derivatives, Neural Inhibition physiology, Neurons physiology, Nucleus Accumbens cytology, Receptors, Dopamine D1 physiology
- Abstract
One of the current hypotheses on dopamine in the physiology of motivation posits that this neurotransmitter regulates filtering and selection of inputs to the nucleus accumbens. The effects of dopamine (100 microM) and the D1-receptor agonist SKF 38393 (20-50 microM) on GABAergic synaptic transmission between pairs of principal cells of rat nucleus accumbens were studied by using simultaneous dual patch-clamp recordings in acutely prepared brain slices. Both compounds attenuated postsynaptic responses induced by presynaptic firing and this effect was reversed by the D1-receptor antagonist SCH 23390 (25 microM). This attenuating effect of dopamine D1-receptors may act to diminish competitive interactions between single projection neurons or ensembles in the nucleus accumbens.
- Published
- 2005
- Full Text
- View/download PDF
35. Creutzfeldt-Jakob disease: Carnoy's fixative improves the immunohistochemistry of the proteinase K-resistant prion protein.
- Author
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Giaccone G, Canciani B, Puoti G, Rossi G, Goffredo D, Iussich S, Fociani P, Tagliavini F, and Bugiani O
- Subjects
- Adult, Aged, Aged, 80 and over, Brain pathology, Creutzfeldt-Jakob Syndrome metabolism, Female, Humans, Male, Middle Aged, Creutzfeldt-Jakob Syndrome pathology, Endopeptidase K metabolism, Fixatives chemistry, Immunohistochemistry, Prions analysis
- Abstract
The neuropathological diagnosis of Creutzfeldt-Jakob disease relies on the immunohistochemical demonstration of the proteinase-K resistant form of the prion protein (PrPres) in the brain tissue. The antigenicity of PrPres is strongly reduced by the formalin solution widely used to fix the tissue, thus the PrPres immunoreactivity is inconsistently detectable in formalin-fixed tissue. A better PrPres immunostaining can be obtained by using Carnoy's fixing solution, which is composed of ethanol, chloroform and acetic acid (6:3:1). PrPres can easily be extracted from Carnoy's-fixed, paraplast-embedded tissue. Accordingly, Carnoy's-fixed tissue can prior to immunolabeling be subjected to proteinase K and guanidine thiocyanate, which respectively eliminate the normal cellular form of prion protein and promote protein denaturation. In comparison with the best protocols for formalin-fixed tissue (i.e.--hydrolytic autoclaving or autoclaving in distilled water followed by formic acid and guanidine thiocyanate), PrPres immunostaining carried out on sections cut from Carnoy's-fixed, paraplast-embedded tissue blocks and subjected to proteinase K and guanidine thiocyanate, proved more successful to detect and map both diffuse and focal PrPres immunoreactivity, and to correlate the immunoreactivity pattern with MV polymorphism at PRNP codon 129 and PrPres banding and glycosylation pattern revealed by Western blot.
- Published
- 2000
- Full Text
- View/download PDF
36. A betaPP peptide carboxyl-terminal to Abeta is neurotoxic.
- Author
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Marcon G, Giaccone G, Canciani B, Cajola L, Rossi G, De Gioia L, Salmona M, Bugiani O, and Tagliavini F
- Subjects
- Animals, Apoptosis, Cell Size drug effects, Cell Survival drug effects, Cells, Cultured, Dose-Response Relationship, Drug, Electrophoresis, Agar Gel, Fetus, Hippocampus drug effects, In Situ Nick-End Labeling, Microscopy, Electron, Mutagenesis, Site-Directed, Neurons cytology, Neurons metabolism, Rats, Amyloid beta-Protein Precursor pharmacology, Amyloid beta-Protein Precursor physiology, Neurons drug effects, Peptide Fragments pharmacology
- Abstract
Extracellular Abeta-amyloid and intraneuronal paired helical filaments (PHFs) composed of tau protein are the neuropathological hallmark of Alzheimer's disease. Abeta is a 39- to 43-residue peptide derived by cleavage of a 695- to 770-amino-acid membrane-associate glycoprotein (termed beta-protein precursor, betaPP). Following the observation that an antiserum to an epitope located between residues 713 and 723 of betaPP770 (ie, the transmembrane region of the betaPP distal to Abeta) labels PHFs and that a synthetic peptide homologous to residues 713 to 730 of betaPP770 (betaPP713-730) is highly fibrillogenic and interacts with tau in vitro, it has been hypothesized that betaPP fragments other than Abeta may feature in the pathogenesis of Alzheimer's disease concurring with neuronal degeneration. To investigate this issue, we have analyzed the effects of the exposure of primary neuronal cultures to the synthetic peptide betaPP713-730. Cultures were prepared from rat hippocampus on embryonic day 17 and incubated with the peptide at 2.5 to 30 micromol/L concentration for 1 to 4 days. Cell viability was compared with that of control cultures exposed to a scrambled sequence of the peptide. A 4-day exposure to 20 micromol/L betaPP713-730 resulted in almost complete neuronal loss, whereas no changes were observed with the scrambled peptide. Degenerating neurons showed DNA fragmentation by agarose gel electrophoresis and apoptotic changes by light and electron microscopy. These findings support the view that betaPP sequences other than Abeta may play a role in nerve cell degeneration in Alzheimer's disease.
- Published
- 1999
- Full Text
- View/download PDF
37. Right bundle branch block, persistent ST segment elevation and sudden cardiac death.
- Author
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Martini B, Nava A, Canciani B, and Thiene G
- Subjects
- Humans, Syndrome, Bundle-Branch Block physiopathology, Death, Sudden, Cardiac, Electrocardiography
- Published
- 1993
- Full Text
- View/download PDF
38. A casual spontaneous mutation as possible cause of the familial form of arrhythmogenic right ventricular cardiomyopathy (arrhythmogenic right ventricular dysplasia).
- Author
-
Canciani B, Nava A, Toso V, Martini B, and Thiene G
- Subjects
- Adolescent, Adult, Arrhythmias, Cardiac complications, Cardiomyopathies complications, Child, Female, Humans, Male, Middle Aged, Mutation, Arrhythmias, Cardiac genetics, Cardiomyopathies genetics
- Abstract
In a family affected by arrhythmogenic right ventricular cardiomyopathy (ARVC) the familial occurrence was investigated. All 14 members of two generations were investigated carefully, and only 2 (father and one son) members were affected. Both subjects had a massive form of the disease with relevant ventricular arrhythmias. Apart from the limitations of having investigated few subjects, this behavior suggests a genetic mutation appearing in the father and transmitted via an autosomal dominant trait.
- Published
- 1992
- Full Text
- View/download PDF
39. Arrhythmia development in a young subject with right ventricular cardiomyopathy (right ventricular dysplasia).
- Author
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Canciani B, Nava A, Martini B, and Buja G
- Subjects
- Adult, Arrhythmias, Cardiac physiopathology, Cardiomyopathies pathology, Electrocardiography, Heart Ventricles, Humans, Male, Myocardium pathology, Arrhythmias, Cardiac complications, Cardiomyopathies complications
- Abstract
In right ventricular cardiomyopathy the relationship between the progression of structural abnormalities and arrhythmia development is not yet well known. This report describes a case in which severe ventricular arrhythmias appeared 3 years after the demonstration of right ventricular (RV) structural and dynamic abnormalities. In this interval of time structural changes were not detectable with the commonly used diagnostic methods, but endocavitary RV late fractionated QRS potentials appeared suggesting the development of an arrhythmic component of the disease.
- Published
- 1991
- Full Text
- View/download PDF
40. Bidirectional tachycardia. A sustained form, not related to digitalis intoxication, in an adult without apparent cardiac disease.
- Author
-
Martini B, Buja GF, Canciani B, and Nava A
- Subjects
- Electrophysiology, Female, Humans, Middle Aged, Vectorcardiography, Digitalis, Electrocardiography, Plants, Medicinal, Plants, Toxic, Tachycardia physiopathology
- Abstract
In this paper we report the first adult case of an "idiopathic" ventricular bidirectional tachycardia (BT), in a 57 year old woman. The tachycardia, at the time of our observation, was incessant in type and had a slightly irregular frequency of about 140 bpm. BT initiated and terminated abruptly, without any temporal relationship to the preceding RR interval, or the QRS morphology. The interval between the two alternating QRS patterns often varied over a wide range of values. The BT could be interrupted only by overdrive atrial and ventricular stimulation, but promptly reappeared as pacing was discontinued. Therapy with quinidine associated with propranolol was effective on a long term trial. The vectorcardiographic analysis and the electrophysiologic investigation demonstrated a ventricular origin of the BT, localizing its site of origin to common myocardial tissue, probably near the two left hemifascicles. Our data could not elucidate the electrogenetic mechanism of this ventricular arrhythmia, because of its chaotic behavior.
- Published
- 1988
- Full Text
- View/download PDF
41. Familial occurrence of right ventricular dysplasia: a study involving nine families.
- Author
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Nava A, Thiene G, Canciani B, Scognamiglio R, Daliento L, Buja G, Martini B, Stritoni P, and Fasoli G
- Subjects
- Adolescent, Adult, Aged, Angiography, Cardiomyopathies diagnosis, Cardiomyopathies pathology, Cause of Death, Child, Echocardiography, Heart Ventricles, Hemodynamics, Humans, Middle Aged, Cardiomyopathies genetics
- Abstract
Right ventricular pathologic involvement, with autopsy evidence of fibrous and fatty infiltration of the right ventricle, was investigated in members of families in which cases of juvenile sudden death had occurred. Seventy-two subjects from nine families were studied. Sixteen died at a young age and 56 are living. Postmortem investigation in 11 cases (mean age at death 24 years) revealed massive replacement of the right ventricular free wall by fat or fibrous tissue. In the 56 living patients clinical examination included an electrocardiogram (ECG) at rest, ambulatory ECG recording, posteroanterior and lateral chest roentgenograms, M-mode and two-dimensional echocardiograms and exercise stress tests. In 14 patients, hemodynamic, angiographic and electrophysiologic studies were also carried out; right ventricular endomyocardial biopsy was performed in four. Structural and dynamic right ventricular impairment was detected in 30 living patients (mean age 25 years), and concomitant mild left ventricular abnormalities were present in 4. In eight of the nine families studied at least two members were affected. Ventricular arrhythmias (Lown grade greater than or equal to 4a) were recorded in more than half of the cases. The data reveal that right ventricular dysplasia shows a familial clustering and causes electrical instability that may place affected subjects at risk of sudden death. The mean age of these subjects suggests that the disease is manifested at a young age with a polymorphic clinical and arrhythmic profile. Finally, because this disease is a primary disorder of the ventricular myocardium, it should be included among the cardiomyopathies.
- Published
- 1988
- Full Text
- View/download PDF
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