英格兰卫生监管机构医疗质量委员会（the Care Quality Commission，CQC）近期判定剑桥市Addenbrooke医院的医疗质量“不完善”，并对其采取了特殊措施。Addenbrooke医院的信誉和医院首席执行官的辞职成为了媒体头条。评论员更是煽风点...英格兰卫生监管机构医疗质量委员会（the Care Quality Commission，CQC）近期判定剑桥市Addenbrooke医院的医疗质量“不完善”，并对其采取了特殊措施。Addenbrooke医院的信誉和医院首席执行官的辞职成为了媒体头条。评论员更是煽风点火，质疑过度管理的意义。随后，CQC发布了一篇名为“Shooting the Messenger”的博客，博客写到：“被监察的医院不应该浪费时间争论监察结果，而是应该承认错误并尽快做出改变。”展开更多
Osteoporosis is a metabolic bone disease with dysregulated coupling between bone resorption and bone formation,which results in decreased bone mineral density.The MEF2C locus,which encodes the transcription factor MAD...Osteoporosis is a metabolic bone disease with dysregulated coupling between bone resorption and bone formation,which results in decreased bone mineral density.The MEF2C locus,which encodes the transcription factor MADS box transcription enhancer factor 2,polypeptide C(MEF2C),is strongly associated with adult osteoporosis and osteoporotic fractures.Although the role of MEF2C in bone and cartilage formation by osteoblasts,osteocytes,and chondrocytes has been studied,the role of MEF2C in osteoclasts,which mediate bone resorption,remains unclear.In this study,we identified MEF2C as a positive regulator of human and mouse osteoclast differentiation.While decreased MEF2C expression resulted in diminished osteoclastogenesis,ectopic expression of MEF2C enhanced osteoclast generation.Using transcriptomic and bioinformatic approaches,we found that MEF2C promotes the RANKL-mediated induction of the transcription factors c-FOS and NFATc1,which play a key role in osteoclastogenesis.Mechanistically,MEF2C binds to FOS regulatory regions to induce c-FOS expression,leading to the activation of NFATC1 and downstream osteoclastogenesis.Inducible deletion of Mef2c in mice resulted in increased bone mass under physiological conditions and protected mice from bone erosion by diminishing osteoclast formation in K/BxN serum induced arthritis,a murine model of inflammatory arthritis.Our findings reveal direct regulation of osteoclasts by MEF2C,thus adding osteoclasts as a cell type in which altered MEF2C expression or function can contribute to pathological bone remodeling.展开更多
文摘英格兰卫生监管机构医疗质量委员会（the Care Quality Commission，CQC）近期判定剑桥市Addenbrooke医院的医疗质量“不完善”，并对其采取了特殊措施。Addenbrooke医院的信誉和医院首席执行官的辞职成为了媒体头条。评论员更是煽风点火，质疑过度管理的意义。随后，CQC发布了一篇名为“Shooting the Messenger”的博客，博客写到：“被监察的医院不应该浪费时间争论监察结果，而是应该承认错误并尽快做出改变。”
文摘Osteoporosis is a metabolic bone disease with dysregulated coupling between bone resorption and bone formation,which results in decreased bone mineral density.The MEF2C locus,which encodes the transcription factor MADS box transcription enhancer factor 2,polypeptide C(MEF2C),is strongly associated with adult osteoporosis and osteoporotic fractures.Although the role of MEF2C in bone and cartilage formation by osteoblasts,osteocytes,and chondrocytes has been studied,the role of MEF2C in osteoclasts,which mediate bone resorption,remains unclear.In this study,we identified MEF2C as a positive regulator of human and mouse osteoclast differentiation.While decreased MEF2C expression resulted in diminished osteoclastogenesis,ectopic expression of MEF2C enhanced osteoclast generation.Using transcriptomic and bioinformatic approaches,we found that MEF2C promotes the RANKL-mediated induction of the transcription factors c-FOS and NFATc1,which play a key role in osteoclastogenesis.Mechanistically,MEF2C binds to FOS regulatory regions to induce c-FOS expression,leading to the activation of NFATC1 and downstream osteoclastogenesis.Inducible deletion of Mef2c in mice resulted in increased bone mass under physiological conditions and protected mice from bone erosion by diminishing osteoclast formation in K/BxN serum induced arthritis,a murine model of inflammatory arthritis.Our findings reveal direct regulation of osteoclasts by MEF2C,thus adding osteoclasts as a cell type in which altered MEF2C expression or function can contribute to pathological bone remodeling.
