Patients with Alzheimer’s disease(AD)often have lower bone mass than healthy individuals.However,the mechanisms underlying this change remain elusive.Previously,we found that Tg2576 mice,an AD animal model that ubiqu...Patients with Alzheimer’s disease(AD)often have lower bone mass than healthy individuals.However,the mechanisms underlying this change remain elusive.Previously,we found that Tg2576 mice,an AD animal model that ubiquitously expresses Swedish mutant amyloid precursor protein(APPswe),shows osteoporotic changes,reduced bone formation,and increased bone resorption.To understand how bone deficits develop in Tg2576 mice,we used a multiplex antibody array to screen for serum proteins that are altered in Tg2576 mice and identified hepcidin,a master regulator of iron homeostasis.We further investigated hepcidin’s function in bone homeostasis and found that hepcidin levels were increased not only in the serum but also in the liver,muscle,and osteoblast(OB)lineage cells in Tg2576 mice at both the mRNA and protein levels.We then generated mice selectively expressing hepcidin in hepatocytes or OB lineage cells,which showed trabecular bone loss and increased osteoclast(OC)-mediated bone resorption.Further cell studies suggested that hepcidin increased OC precursor proliferation and differentiation by downregulating ferroportin(FPN)expression and increasing intracellular iron levels.In OB lineage cells,APPswe enhanced hepcidin expression by inducing ER stress and increasing OC formation,in part through hepcidin.Together,these results suggest that increased hepcidin expression in hepatocytes and OB lineage cells in Tg2576 mice contributes to enhanced osteoclastogenesis and trabecular bone loss,identifying the hepcidin-FPN-iron axis as a potential therapeutic target to prevent AD-associated bone loss.展开更多
In this study,perforated cannulated magnesium(Mg)hip stents were fabricated via modified Mg injection molding and conventional machining,respectively.Additionally,the stent canal was filled with paraffin to simulate i...In this study,perforated cannulated magnesium(Mg)hip stents were fabricated via modified Mg injection molding and conventional machining,respectively.Additionally,the stent canal was filled with paraffin to simulate injection of biomaterials.The microstructure,mechanical performance,corrosion behavior,and biocompatibility were comparably studied.Scanning electron microscopy(SEM)and energy dispersive spectroscopy(EDS)showed higher affinity of interstitial element such as oxygen and carbon as consequences of routine molding process.After immersion in SBF,machining stents showed reduced degradation rate and increased deposition of calcium phosphate compared to molding stents.Corrosion resistance was improved via paraffin-filling.Consistently,the hemolysis and in vitro osteoblast cell culture models showed favourable biocompatibility in machining stents compared to molding ones,which was improved by paraffin-filling treatment as well.These results implied that the feasibility of the prepared machining stents as the potential in vivo orthopaedic application where slower degradation is required,which could be enhanced by designing canal-filling injection of biomaterials as well.展开更多
Over the past few decades,China’s pension system has evolved from separate schemes almost exclusively for urban and public sector workers to one with broad national coverage.In a similar time-frame,successive Austral...Over the past few decades,China’s pension system has evolved from separate schemes almost exclusively for urban and public sector workers to one with broad national coverage.In a similar time-frame,successive Australian governments have introduced reforms to Australia’s retirement income arrangements in an attempt to increase retirement savings and address age-related pressures on the financing of the publicly provided age pension.This paper compares,contrasts and assesses the pension systems in China and Australia.Although China and Australia are at different stages of economic development and demographic transition and operate quite different pension systems,there are lessons to be learned from each other.展开更多
基金supported in part by grants from the National Institutes of Health(AG051773)the U.S.Department of Veterans Affairs(BX000838)by the Meisel family and InMotion in Cleveland,Ohio.
文摘Patients with Alzheimer’s disease(AD)often have lower bone mass than healthy individuals.However,the mechanisms underlying this change remain elusive.Previously,we found that Tg2576 mice,an AD animal model that ubiquitously expresses Swedish mutant amyloid precursor protein(APPswe),shows osteoporotic changes,reduced bone formation,and increased bone resorption.To understand how bone deficits develop in Tg2576 mice,we used a multiplex antibody array to screen for serum proteins that are altered in Tg2576 mice and identified hepcidin,a master regulator of iron homeostasis.We further investigated hepcidin’s function in bone homeostasis and found that hepcidin levels were increased not only in the serum but also in the liver,muscle,and osteoblast(OB)lineage cells in Tg2576 mice at both the mRNA and protein levels.We then generated mice selectively expressing hepcidin in hepatocytes or OB lineage cells,which showed trabecular bone loss and increased osteoclast(OC)-mediated bone resorption.Further cell studies suggested that hepcidin increased OC precursor proliferation and differentiation by downregulating ferroportin(FPN)expression and increasing intracellular iron levels.In OB lineage cells,APPswe enhanced hepcidin expression by inducing ER stress and increasing OC formation,in part through hepcidin.Together,these results suggest that increased hepcidin expression in hepatocytes and OB lineage cells in Tg2576 mice contributes to enhanced osteoclastogenesis and trabecular bone loss,identifying the hepcidin-FPN-iron axis as a potential therapeutic target to prevent AD-associated bone loss.
基金supported by Theme-based Research Scheme(Ref No.T13-402/17-N)Collaborative Research Fund(C402617W)from the Research Grants Council of the Hong Kong Special Administrative Region,ChinaInnovation and Technology Fund(ITS/208/18FX)from the Innovation and Technology Commission of Hong Kong。
文摘In this study,perforated cannulated magnesium(Mg)hip stents were fabricated via modified Mg injection molding and conventional machining,respectively.Additionally,the stent canal was filled with paraffin to simulate injection of biomaterials.The microstructure,mechanical performance,corrosion behavior,and biocompatibility were comparably studied.Scanning electron microscopy(SEM)and energy dispersive spectroscopy(EDS)showed higher affinity of interstitial element such as oxygen and carbon as consequences of routine molding process.After immersion in SBF,machining stents showed reduced degradation rate and increased deposition of calcium phosphate compared to molding stents.Corrosion resistance was improved via paraffin-filling.Consistently,the hemolysis and in vitro osteoblast cell culture models showed favourable biocompatibility in machining stents compared to molding ones,which was improved by paraffin-filling treatment as well.These results implied that the feasibility of the prepared machining stents as the potential in vivo orthopaedic application where slower degradation is required,which could be enhanced by designing canal-filling injection of biomaterials as well.
文摘Over the past few decades,China’s pension system has evolved from separate schemes almost exclusively for urban and public sector workers to one with broad national coverage.In a similar time-frame,successive Australian governments have introduced reforms to Australia’s retirement income arrangements in an attempt to increase retirement savings and address age-related pressures on the financing of the publicly provided age pension.This paper compares,contrasts and assesses the pension systems in China and Australia.Although China and Australia are at different stages of economic development and demographic transition and operate quite different pension systems,there are lessons to be learned from each other.