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...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.展开更多
Aim:This animal study aims to examine the efficacy and safety of poly-D,L-lactic acid(PDLLA)microspheres as subdermal fillers.Methods:Thirty 2-week-old male Sprague Dawley rats were used as test animals,and 0.5 mL fil...Aim:This animal study aims to examine the efficacy and safety of poly-D,L-lactic acid(PDLLA)microspheres as subdermal fillers.Methods:Thirty 2-week-old male Sprague Dawley rats were used as test animals,and 0.5 mL filler solutions were injected into the subdermal tissues on their backs.Groups of five rats were randomly selected and sacrificed for examination on the 2nd,4th,8th,12th,16th,and 20th weeks after injection.Clinical and histological examinations were performed via the hematoxyline-eosin and immunohistochemical(IHC)staining of injected sites after collecting the injected masses.The body weights of the rats were measured,and the presence of filler substance in other organs was determined.Results:Injected volumes were stable from the 2nd to the 20th week after injection,and no abnormalities were observed around the injection sites.The injected substance did not migrate to the surrounding tissues.In IHC staining experiments,myofibroblasts were observed from the 2nd week,and collagen was detected from the 4th week.Myofibroblast was observed in the spaces between and inside the microspheres in the 8th week after injection,whereas type I collagen was found between and inside the microspheres at 8th and 12th weeks,respectively.Conclusion:The animal experiments confirm the efficacy and safety of injectable PDLLA as a subdermal filler.展开更多
基金supported by grants from the National Research Foundation of Korea(RS-2023-00217798 and 2021R1A2C3003675 to S.Y.L.)by the Korea Basic Science Institute National Research Facilities&Equipment Center grant(2019R1A6C1010020).M.K.was supported in part by scholarship from Ewha Womans University.
文摘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.
基金This work was supported by Regen Biotech,Inc.,Seoul,South Korea.
文摘Aim:This animal study aims to examine the efficacy and safety of poly-D,L-lactic acid(PDLLA)microspheres as subdermal fillers.Methods:Thirty 2-week-old male Sprague Dawley rats were used as test animals,and 0.5 mL filler solutions were injected into the subdermal tissues on their backs.Groups of five rats were randomly selected and sacrificed for examination on the 2nd,4th,8th,12th,16th,and 20th weeks after injection.Clinical and histological examinations were performed via the hematoxyline-eosin and immunohistochemical(IHC)staining of injected sites after collecting the injected masses.The body weights of the rats were measured,and the presence of filler substance in other organs was determined.Results:Injected volumes were stable from the 2nd to the 20th week after injection,and no abnormalities were observed around the injection sites.The injected substance did not migrate to the surrounding tissues.In IHC staining experiments,myofibroblasts were observed from the 2nd week,and collagen was detected from the 4th week.Myofibroblast was observed in the spaces between and inside the microspheres in the 8th week after injection,whereas type I collagen was found between and inside the microspheres at 8th and 12th weeks,respectively.Conclusion:The animal experiments confirm the efficacy and safety of injectable PDLLA as a subdermal filler.
