RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts

Mature osteoclasts degrade bone matrix by exocytosis of active proteases from secretory lysosomes through a ruffled border.However,the molecular mechanisms underlying lysosomal trafficking and secretion in osteoclasts remain largely unknown.Here,we show with GeneChip analysis that RUN and FYVE domain-containing protein 4(RUFY4)is strongly upregulated during osteoclastogenesis.Mice lacking Rufy4 exhibited a high trabecular bone mass phenotype with abnormalities in osteoclast function in vivo.Furthermore,deleting Rufy4 did not affect osteoclast differentiation,but inhibited bone-resorbing activity due to disruption in the acidic maturation of secondary lysosomes,their trafficking to the membrane,and their secretion of cathepsin K into the extracellular space.Mechanistically,RUFY4 promotes late endosome-lysosome fusion by acting as an adaptor protein between Rab7 on late endosomes and LAMP2 on primary lysosomes.Consequently,Rufy4-deficient mice were highly protected from lipopolysaccharide-and ovariectomy-induced bone loss.Thus,RUFY4 plays as a new regulator in osteoclast activity by mediating endo-lysosomal trafficking and have a potential to be specific target for therapies against bone-loss diseases such as osteoporosis.

不同肌肉组选择导出模块对组间肌电反复性的影响（英文）

目的评价组间肌电反复性对不同肌肉组选择导出模块的影响。方法记录12名参与实验者在自选速度下行走时16块肌肉的肌电图。用组内相关系数评价每个步行周期的肌肉兴奋度和肌肉模块。依据肌肉兴奋度的反复性,区分出3种类型的肌肉组。结果可靠肌肉组显示出较高的组内相关系数(>0.4),而全身肌肉组和混合肌肉组显示出较低的组内相关系数(<0.4)。3种类型肌肉组比较,可靠肌肉组分析得出的模块具有最好的反复性,全身肌肉组和混合肌肉组的反复性较低。结论具有较高可靠性的肌肉兴奋性能够得出较一致的模块。得出一致模块的方法非常重要,尤其是在依靠肌肉兴奋性反馈而改变的运动模式中。