General Administration of Quality Supervision,Inspection and Quarantine of P.R.China has approved the following 8 national measuring verification regulations in 2010 and publicize now.
General Administration of Quality Supervision,Inspection and Quarantine of P.R.China has approved the following 11 national measuring verification regulations in 2008 and publicize now.
General Administration of Quality Supervision,Inspection and Quarantine of P.R.China hasapproved the following 24 national measuring verification regulations in 2008 and publicize now.
General Administration of Quality Supervision,Inspection and Quarantine of P.R.China has approved the following 10 national measuring verification regulations in 2008 and publicize now.
Mutations in the liver/bone/kidney alkaline phosphatase(Alpl) gene cause hypophosphatasia(HPP) and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development. However, how and where...Mutations in the liver/bone/kidney alkaline phosphatase(Alpl) gene cause hypophosphatasia(HPP) and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development. However, how and where Alpl acts in bone ageing is largely unknown. Here, we determined that ablation of Alpl induces prototypical premature bone ageing characteristics, including bone mass loss and marrow fat gain coupled with elevated expression of p16INK4A(p16) and p53 due to senescence and impaired differentiation in mesenchymal stem cells(MSCs). Mechanistically, Alpl deficiency in MSCs enhances ATP release and reduces ATP hydrolysis. Then, the excessive extracellular ATP is, in turn, internalized by MSCs and causes an elevation in the intracellular ATP level, which consequently inactivates the AMPKα pathway and contributes to the cell fate switch of MSCs. Reactivating AMPKα by metformin treatment successfully prevents premature bone ageing in Alpl+/-mice by improving the function of endogenous MSCs.These results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKα alterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option.展开更多
Dear Editor, Although various components of the Wnt/β-catenin pathway have been investigated, there are conflicting reports on the roles of Wnt/β-catenin signaling in oligodendrogenesis and differentiation. For inst...Dear Editor, Although various components of the Wnt/β-catenin pathway have been investigated, there are conflicting reports on the roles of Wnt/β-catenin signaling in oligodendrogenesis and differentiation. For instance, the △Exon3 mutation of β-catenin[14], which stabilizes β-catenin by deletion of the phosphorylation site for the destruction complex, significantly inhibits the differentiation of oligodendrocytes, but knockout of β-catenin also delays it.展开更多
文摘General Administration of Quality Supervision,Inspection and Quarantine of P.R.China has approved the following 8 national measuring verification regulations in 2010 and publicize now.
文摘General Administration of Quality Supervision,Inspection and Quarantine of P.R.China has approved the following 11 national measuring verification regulations in 2008 and publicize now.
文摘General Administration of Quality Supervision,Inspection and Quarantine of P.R.China hasapproved the following 24 national measuring verification regulations in 2008 and publicize now.
文摘General Administration of Quality Supervision,Inspection and Quarantine of P.R.China has approved the following 10 national measuring verification regulations in 2008 and publicize now.
基金financially supported by grants from the Nature Science Foundation of China (81620108007)National Key Research and Development Program of China (2016YFC1101400)+1 种基金Nature Science Foundation of China (31571532, 31601099)National Institutes of Health, Department of Health and Human Services (R01DE017449 to S.S.)
文摘Mutations in the liver/bone/kidney alkaline phosphatase(Alpl) gene cause hypophosphatasia(HPP) and early-onset bone dysplasia,suggesting that this gene is a key factor in human bone development. However, how and where Alpl acts in bone ageing is largely unknown. Here, we determined that ablation of Alpl induces prototypical premature bone ageing characteristics, including bone mass loss and marrow fat gain coupled with elevated expression of p16INK4A(p16) and p53 due to senescence and impaired differentiation in mesenchymal stem cells(MSCs). Mechanistically, Alpl deficiency in MSCs enhances ATP release and reduces ATP hydrolysis. Then, the excessive extracellular ATP is, in turn, internalized by MSCs and causes an elevation in the intracellular ATP level, which consequently inactivates the AMPKα pathway and contributes to the cell fate switch of MSCs. Reactivating AMPKα by metformin treatment successfully prevents premature bone ageing in Alpl+/-mice by improving the function of endogenous MSCs.These results identify a previously unknown role of Alpl in the regulation of ATP-mediated AMPKα alterations that maintain MSC stemness and prevent bone ageing and show that metformin offers a potential therapeutic option.
基金supported by the National Basic Research Development Program of China (2013CB531303, 2012CB910402)the National Natural Science Foundation of China (31101642, 31372150)+1 种基金the Science and Technology Key Project of Zhejiang Province, China (2011C13030)the National Institutes of Health, USA (R01-NS37717)
文摘Dear Editor, Although various components of the Wnt/β-catenin pathway have been investigated, there are conflicting reports on the roles of Wnt/β-catenin signaling in oligodendrogenesis and differentiation. For instance, the △Exon3 mutation of β-catenin[14], which stabilizes β-catenin by deletion of the phosphorylation site for the destruction complex, significantly inhibits the differentiation of oligodendrocytes, but knockout of β-catenin also delays it.
