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Osteoporosis and obesity: Role of Wnt pathway in human and murine models 被引量:20
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作者 Graziana Colaianni Giacomina Brunetti +2 位作者 maria felicia faienza Silvia Colucci maria Grano 《World Journal of Orthopedics》 2014年第3期242-246,共5页
Studies concerning the pathophysiological connection between obesity and osteoporosis are currently an intriguing area of research.Although the onset of these two diseases can occur in a different way,recent studies h... Studies concerning the pathophysiological connection between obesity and osteoporosis are currently an intriguing area of research.Although the onset of these two diseases can occur in a different way,recent studies have shown that obesity and osteoporosis share common genetic and environmental factors.Despite being a risk factor for health,obesity has traditionally been considered positive to bone because of beneficial effect of mechanical loading,exerted by high body mass,on bone formation.However,contrasting studies have not achieved a clear consensus,suggesting instead that excessive fat mass derived from obesity condition may not protect against osteoporosis or,even worse,could be rather detrimental to bone.On the other hand,it is hitherto better established that,since adipocytes and osteoblasts are derived from a common mesenchymal stem cell precursor,molecules that lead to osteoblastogenesis inhibit adipogenesis and vice versa.Here we will discuss the role of the key molecules regulating adipocytes and osteoblasts differentiation,which are peroxisome proliferators activated receptor-γand Wnts,respectively.In particular,wewill focus on the role of both canonical and non-canonical Wnt signalling,involved in mesenchymal cell fate regulation.Moreover,at present there are no experimental data that relate any influence of the Wnt inhibitor Sclerostin to adipogenesis,although it is well known its role on bone metabolism.In addition,the most common pathological condition in which there is a simultaneous increase of adiposity and decrease of bone mass is menopause.Given that postmenopausal women have high Sclerostin level inversely associated with circulating estradiol level and since the sex hormone replacement therapy has proved to be effective in attenuating bone loss and reversing menopause-related obesity,we hypothesize that Sclerostin contribution in adipogenesis could be an active focus of research in the coming years. 展开更多
关键词 OSTEOPOROSIS OBESITY Bone FAT Wnt PEROXISOME proliferators activated receptor-γ DICKKOPF SCLEROSTIN
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Mechanisms of altered bone remodeling in children with type 1 diabetes 被引量:7
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作者 Giacomina Brunetti Gabriele D'Amato +2 位作者 Stefania De Santis maria Grano maria felicia faienza 《World Journal of Diabetes》 SCIE 2021年第7期997-1009,共13页
Bone loss associated with type 1 diabetes mellitus(T1DM)begins at the onset of the disease,already in childhood,determining a lower bone mass peak and hence a greater risk of osteoporosis and fractures later in life.T... Bone loss associated with type 1 diabetes mellitus(T1DM)begins at the onset of the disease,already in childhood,determining a lower bone mass peak and hence a greater risk of osteoporosis and fractures later in life.The mechanisms underlying diabetic bone fragility are not yet completely understood.Hyperglycemia and insulin deficiency can affect the bone cells functions,as well as the bone marrow fat,thus impairing the bone strength,geometry,and microarchitecture.Several factors,like insulin and growth hormone/insulin-like growth factor 1,can control bone marrow mesenchymal stem cell commitment,and the receptor activator of nuclear factor-κB ligand/osteoprotegerin and Wnt-b catenin pathways can impair bone turnover.Some myokines may have a key role in regulating metabolic control and improving bone mass in T1DM subjects.The aim of this review is to provide an overview of the current knowledge of the mechanisms underlying altered bone remodeling in children affected by T1DM. 展开更多
关键词 Type 1 diabetes CHILDREN Bone remodeling OSTEOCLASTS OSTEOBLASTS
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Type 2 diabetes and bone fragility in children and adults 被引量:2
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作者 maria felicia faienza Paola Pontrelli Giacomina Brunetti 《World Journal of Diabetes》 SCIE 2022年第11期900-911,共12页
Type 2 diabetes(T2D)is a global epidemic disease.The prevalence of T2D in adolescents and young adults is increasing alarmingly.The mechanisms leading to T2D in young people are similar to those in older patients.Howe... Type 2 diabetes(T2D)is a global epidemic disease.The prevalence of T2D in adolescents and young adults is increasing alarmingly.The mechanisms leading to T2D in young people are similar to those in older patients.However,the severity of onset,reduced insulin sensitivity and defective insulin secretion can be different in subjects who develop the disease at a younger age.T2D is associated with different complications,including bone fragility with consequent susceptibility to fractures.The purpose of this systematic review was to describe T2D bone fragility together with all the possible involved pathways.Numerous studies have reported that patients with T2D show preserved,or even increased,bone mineral density compared with controls.This apparent paradox can be explained by the altered bone quality with increased cortical bone porosity and compromised mechanical properties.Furthermore,reduced bone turnover has been described in T2D with reduced markers of bone formation and resorption.These findings prompted different researchers to highlight the mechanisms leading to bone fragility,and numerous critical altered pathways have been identified and studied.In detail,we focused our attention on the role of microvascular disease,advanced glycation end products,the senescence pathway,the Wnt/β-catenin pathway,the osteoprotegerin/receptor-activator of nuclear factor kappa B ligand,osteonectin and fibroblast growth factor 23.The understanding of type 2 myeloid bone fragility is an important issue as it could suggest possible interventions for the prevention of poor bone quality in T2D and/or how to target these pathways when bone disease is clearly evident. 展开更多
关键词 Type 2 diabetes Bone remodeling CYTOKINES Bone fragility Bone mineral density Chronic kidney disease
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An update on the role of RANKL-RANK/osteoprotegerin and WNT-β-catenin signaling pathways in pediatric diseases 被引量:4
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作者 Giacomina Brunetti Gabriele D'Amato +5 位作者 mariancgela Chiarito Apollonia Tullo Graziana Colaianni Silvia Colucci maria Grano maria felicia faienza 《World Journal of Pediatrics》 SCIE CAS CSCD 2019年第1期4-11,共8页
Background Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs),the bone-reabsorbing cells,and osteoblasts (OBs),and the bone-forming cells.This equilibrium is regulated by numerous ... Background Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs),the bone-reabsorbing cells,and osteoblasts (OBs),and the bone-forming cells.This equilibrium is regulated by numerous cytokines,but it has been largely demonstrated that the RANK/RANKL/osteoprotegerin and Wnt/β-catenin pathways play a key role in the control of osteoclastogenesis and osteoblastogenesis,respectively.The pro-osteoblastogenic activity of the Wnt/β-catenin can be inhibited by sclerostin and Dickkopf-1 (DKK-1).RANKL,sclerostin and DKKs-1 are often up-regulated in bone diseases,and they are the target of new monoclonal antibodies.Data sources The authors performed a systematic literature search in PubMed and EMBASE to June 2018,reviewed and selected articles,based on pre-determined selection criteria.Results We re-evaluated the role of RANKL,osteoprotegerin,sclerostin and DKK-1 in altered bone remodeling associated with some inherited and acquired pediatric diseases,such as type 1 diabetes mellitus (T1DM),alkaptonuria (AKU),hemophilia A,osteogenesis imperfecta (OI),21-hydroxylase deficiency (21 OH-D) and Prader-Willi syndrome (PWS).To do so,we considered recent clinical studies done on pediatric patients in which the roles of RANKL-RANK/osteoprotegerin and WNT-β-catenin signaling pathways have been investigated,and for which innovative therapies for the treatment of osteopenia/osteoporosis are being developed.Conclusions The case studies taken into account for this review demonstrated that quite frequently both bone reabsorbing and bone deposition are impaired in pediatric diseases.Furthermore,for some of them,bone damage began in childhood but only manifested with age.The use of denosumab could represent a valid alternative therapeutic approach to improve bone health in children,although further studies need to be carried out. 展开更多
关键词 RANKL-RANK/Osteoprotegerin WNT-β-catenin signaling PEDIATRIC diseases
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Childhood obesity, cardiovascular and liver health: a growing epidemic with age 被引量:1
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作者 maria felicia faienza mariangela Chiarito +5 位作者 Emilio Molina-Molina Harshitha Shanmugam Frank Lammert Marcin Krawczyk Gabriele D'Amato Piero Portincasa 《World Journal of Pediatrics》 SCIE CAS CSCD 2020年第5期438-445,共8页
Background The frequency of childhood obesity has increased over the last 3 decades,and the trend constitutes a worrisome epidemic worldwide.With the raising obesity risk,key aspects to consider are accurate body mass... Background The frequency of childhood obesity has increased over the last 3 decades,and the trend constitutes a worrisome epidemic worldwide.With the raising obesity risk,key aspects to consider are accurate body mass index classification,as well as metabolic and cardiovascular,and hepatic consequences.Data sources The authors performed a systematic literature search in PubMed and EMBASE,using selected key words(obesity,childhood,cardiovascular,liver health).In particular,they focused their search on papers evaluating the impact of obesity on cardiovascular and liver health.Results We evaluated the current literature dealing with the impact of excessive body fat accumulation in childhood and across adulthood,as a predisposing factor to cardiovascular and hepatic alterations.We also evaluated the impact of physical and dietary behaviors starting from childhood on cardio-metabolic consequences.Conclusions The epidemic of obesity and obesity-related comorbidities worldwide raises concerns about the impact of early abnormalities during childhood and adolescence.Two key abnormalities in this context include cardiovascular diseases,and non-alcoholic fatty liver disease.Appropriate metabolic screenings and associated comorbidities should start as early as possible in obese children and adolescents.Nevertheless,improving dietary intake and increasing physical activity performance are to date the best therapeutic tools in children to weaken the onset of obesity,cardiovascular diseases,and diabetes risk during adulthood. 展开更多
关键词 CARDIOVASCULAR CHILDHOOD LIVER HEALTH Obesity
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Cardiovascular dysfunction and vitamin D status in childhood acute lymphoblastic leukemia survivors
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作者 Paola Muggeo Vito Michele Rosario Muggeo +7 位作者 Paola Giordano Maurizio Delvecchio maria Altomare Chiara Novielli Marco Matteo Ciccone Gabriele D'Amato maria felicia faienza Nicola Santoro 《World Journal of Pediatrics》 SCIE CAS CSCD 2019年第5期465-470,共6页
Background Vitamin D(25-OHD)has a role in bone health after treatment for cancer.25-OHD deficiency has been associated with risk factors for cardiovascular disease,but no data focusing on this topic in childhood cance... Background Vitamin D(25-OHD)has a role in bone health after treatment for cancer.25-OHD deficiency has been associated with risk factors for cardiovascular disease,but no data focusing on this topic in childhood cancer survivors have been published.We investigated the 25-OHD status in children treated for acute lymphoblastic leukemia(ALL),and evaluated its influence on vascular function.Methods 25-OHD levels were evaluated in 52 ALL survivors and 40 matched healthy controls.Patients were grouped according to 25-OHD level(<20 ng/m or≥20 ng/ml).Auxological parameters,biochemical and hemostatic markers of endothelial function(AD,HMW-AD,ET-1,vWFAg,TAT,D-dimers,Fbg,and hs-CRP),ultrasound markers of vascular endothelial function(flow-mediated dilatation,FMD,common carotid intima-media thickness,C-IMT,and antero-posterior diameter of infra-renal abdominal aorta,APAO)were evaluated in the patients.Results Cases showed higher prevalence of 25-OHD deficiency than controls(p=0.002).In univariate analysis via mean comparisons,25-OHD deficient(<20 ng/ml)patients showed higher C-IMT values compared to the 25-OHD non-deficient(≥20 ng/ml)group(P=0.023).Significant differences were also found for ET-1(P=0.035)and AD-HMW(P=0.015).In the multiple regression models controlling for some confounders,25-OHD still was associated with C-IMT(P=0.0163),ET-1(P=0.0077),and AD-HMW(P=0.0008).Conclusions Childhood ALL survivors show higher prevalence of 25-OHD deficiency as compared to controls.The 25-OHD levels appear to be linked to indicators of endothelial and vascular dysfunction.Careful monitoring of 25-OHD balance may help to prevent cardiovascular diseases in childhood ALL survivors,characterized by high cardiovascular risk. 展开更多
关键词 Acute lymphoblastic leukemia Cardiovascular disease C-IMT Vascular ultrasound studies Vitamin D
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