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
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
文摘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.
文摘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.
