Objective Despite the potential therapeutic approaches of bone marrow-derived mesenchymal stem cells(BMSCs)in orthopaedic,their applications are hampered by harsh oxidative stress conditions after transplantation.In t...Objective Despite the potential therapeutic approaches of bone marrow-derived mesenchymal stem cells(BMSCs)in orthopaedic,their applications are hampered by harsh oxidative stress conditions after transplantation.In this study,the antiapoptotic and anti-oxidative properties of lithospermic acid(LSA)on BMSCs exposed to hydrogen peroxide(H2O2)were investigated.Methods In the present study,we used H2O2 to induce oxidative injury on BMSCs.Reactive oxygen species(ROS)staining and superoxide dismutase(SOD)assay were performed.The expression levels of phosphorylated(p)-Akt,Bcl-2-associated X protein(Bax)and B-cell lymphoma 2(Bcl-2)were measured by Western blotting.Results LSA can significantly reduce H2O2-induced chromatin condensation and intracellular ROS levels,enhance the activity of SOD.Moreover,it can alleviate H2O2-induced apoptosis by upregulating Bcl-2 and p-Akt,down-regulating Bax,which was blocked by the PI3K inhibitor,LY294002.Conclusions Our results demonstrated that pretreatment with LSA could attenuate oxidative stress-induced apoptosis in BMSCs,which may be related with anti-oxidant properties and partly via modulating PI3K/Akt pathway,suggesting that pharmacologically manipulating BMSCs with LSA could be a promising drug to increase cell survival for BMSCs transplantation in musculoskeletal disorders of orthopaedic.展开更多
MSC transplantation has been explored as a new clinical approach to stem cell-based therapies for bone diseases in regenerative medicine due to their osteogenic capability. However, only a small population of implante...MSC transplantation has been explored as a new clinical approach to stem cell-based therapies for bone diseases in regenerative medicine due to their osteogenic capability. However, only a small population of implanted MSC could successfully reach the injured areas. Therefore, enhancing MSC migration could be a beneficial strategy to improve the therapeutic potential of cell transplantation. Catharmus tinctorius volatile oil(CTVO) was found to facilitate MSC migration. Further exploration of the underlying molecular mechanism participating in the pro-migratory ability may provide a novel strategy to improve MSC transplantation efficacy. This study indicated that CTVO promotes MSC migration through enhancing ROCK2 mRNA and protein expressions. MSC migration induced by CTVO was blunted by ROCK2 inhibitor, which also decreased myosin light chain(MLC) phosphorylation.Meanwhile, the si RNA for ROCK2 inhibited the effect of CTVO on MSC migration ability and attenuated MLC phosphorylation,suggesting that CTVO may promote BMSC migration via the ROCK2/MLC signaling. Taken together, this study indicates that C.tinctorius volatile oil could enhance MSC migration via ROCK2/MLC signaling in vitro. C. tinctorius volatile oil-targeted therapy could be a beneficial strategy to improve the therapeutic potential of cell transplantation for bone diseases in regenerative medicine.展开更多
基金the funding support from the National Natural Science Foundation of China(No.81574005and No.81874478)
文摘Objective Despite the potential therapeutic approaches of bone marrow-derived mesenchymal stem cells(BMSCs)in orthopaedic,their applications are hampered by harsh oxidative stress conditions after transplantation.In this study,the antiapoptotic and anti-oxidative properties of lithospermic acid(LSA)on BMSCs exposed to hydrogen peroxide(H2O2)were investigated.Methods In the present study,we used H2O2 to induce oxidative injury on BMSCs.Reactive oxygen species(ROS)staining and superoxide dismutase(SOD)assay were performed.The expression levels of phosphorylated(p)-Akt,Bcl-2-associated X protein(Bax)and B-cell lymphoma 2(Bcl-2)were measured by Western blotting.Results LSA can significantly reduce H2O2-induced chromatin condensation and intracellular ROS levels,enhance the activity of SOD.Moreover,it can alleviate H2O2-induced apoptosis by upregulating Bcl-2 and p-Akt,down-regulating Bax,which was blocked by the PI3K inhibitor,LY294002.Conclusions Our results demonstrated that pretreatment with LSA could attenuate oxidative stress-induced apoptosis in BMSCs,which may be related with anti-oxidant properties and partly via modulating PI3K/Akt pathway,suggesting that pharmacologically manipulating BMSCs with LSA could be a promising drug to increase cell survival for BMSCs transplantation in musculoskeletal disorders of orthopaedic.
基金supported by the National Nature Science Foundation of China(Nos.81503593,81273783,and 81473699)Guangdong Science and Technology Department(No.2014A020221055)the Natural Science Foundation of Guangdong Province(Nos.2016A030313649 and 2017A030313729)
文摘MSC transplantation has been explored as a new clinical approach to stem cell-based therapies for bone diseases in regenerative medicine due to their osteogenic capability. However, only a small population of implanted MSC could successfully reach the injured areas. Therefore, enhancing MSC migration could be a beneficial strategy to improve the therapeutic potential of cell transplantation. Catharmus tinctorius volatile oil(CTVO) was found to facilitate MSC migration. Further exploration of the underlying molecular mechanism participating in the pro-migratory ability may provide a novel strategy to improve MSC transplantation efficacy. This study indicated that CTVO promotes MSC migration through enhancing ROCK2 mRNA and protein expressions. MSC migration induced by CTVO was blunted by ROCK2 inhibitor, which also decreased myosin light chain(MLC) phosphorylation.Meanwhile, the si RNA for ROCK2 inhibited the effect of CTVO on MSC migration ability and attenuated MLC phosphorylation,suggesting that CTVO may promote BMSC migration via the ROCK2/MLC signaling. Taken together, this study indicates that C.tinctorius volatile oil could enhance MSC migration via ROCK2/MLC signaling in vitro. C. tinctorius volatile oil-targeted therapy could be a beneficial strategy to improve the therapeutic potential of cell transplantation for bone diseases in regenerative medicine.
