YAP（yes-associated protein） is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone h...YAP（yes-associated protein） is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone homeostasis remains controversial. Here we provide evidence for YAP＇s function in promoting osteogenesis, suppressing adipogenesis, and thus maintaining bone homeostasis.YAP is selectively expressed in osteoblast（OB）-lineage cells. Conditionally knocking out Yap in the OB lineage in mice reduces cell proliferation and OB differentiation and increases adipocyte formation, resulting in a trabecular bone loss. Mechanistically, YAP interacts with β-catenin and is necessary for maintenance of nuclear β-catenin level and Wnt/β-catenin signaling. Expression of β-catenin in YAP-deficient BMSCs（bone marrow stromal cells） diminishes the osteogenesis deficit. These results thus identify YAP-β-catenin as an important pathway for osteogenesis during adult bone remodeling and uncover a mechanism underlying YAP regulation of bone homeostasis.展开更多
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
Al2O3 dispersion-strengthened copper alloy was prepared by reactive synthesis and spark plasma sintering（SPS） process. Studies show that nano-sized c-Al2O3 particles with 27.4 nm mean size and 50-nm interval are hom...Al2O3 dispersion-strengthened copper alloy was prepared by reactive synthesis and spark plasma sintering（SPS） process. Studies show that nano-sized c-Al2O3 particles with 27.4 nm mean size and 50-nm interval are homogeneously distributed in copper matrix. The density of SPS alloy is about 99 %, meanwhile, the electrical conductivity of sintered alloy is 72 % IACS and the Rockwell hardness can reach to HRB 91.展开更多
基金supported in part by grants from the National Institutes of Health(AG051773)and VA(BX000838)
文摘YAP（yes-associated protein） is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone homeostasis remains controversial. Here we provide evidence for YAP＇s function in promoting osteogenesis, suppressing adipogenesis, and thus maintaining bone homeostasis.YAP is selectively expressed in osteoblast（OB）-lineage cells. Conditionally knocking out Yap in the OB lineage in mice reduces cell proliferation and OB differentiation and increases adipocyte formation, resulting in a trabecular bone loss. Mechanistically, YAP interacts with β-catenin and is necessary for maintenance of nuclear β-catenin level and Wnt/β-catenin signaling. Expression of β-catenin in YAP-deficient BMSCs（bone marrow stromal cells） diminishes the osteogenesis deficit. These results thus identify YAP-β-catenin as an important pathway for osteogenesis during adult bone remodeling and uncover a mechanism underlying YAP regulation of bone homeostasis.
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financially supported by the National Natural Science Foundation of China (No. 5043202)
文摘Al2O3 dispersion-strengthened copper alloy was prepared by reactive synthesis and spark plasma sintering（SPS） process. Studies show that nano-sized c-Al2O3 particles with 27.4 nm mean size and 50-nm interval are homogeneously distributed in copper matrix. The density of SPS alloy is about 99 %, meanwhile, the electrical conductivity of sintered alloy is 72 % IACS and the Rockwell hardness can reach to HRB 91.
