Joint replacement surgery is one of the orthopedic surgeries with high successful rates;however,wear debris generated from prostheses can ultimately lead to periprosthetic osteolysis and failure of the implant.The imp...Joint replacement surgery is one of the orthopedic surgeries with high successful rates;however,wear debris generated from prostheses can ultimately lead to periprosthetic osteolysis and failure of the implant.The implant-derived particulate debris such as ultrahigh molecular weight polyethylene(UHMWPE)can initiate the local immune response and recruit monocytic cells to phagocytose particles for generating reactive oxygen species(ROS).ROS induces osteoclastogenesis and macrophages to secrete cytokines which ultimately promote the development of osteolysis.In this work,we develop the few-layered Nb_(2)C(FNC)as an antioxidant which possesses the feature of decreasing the production of cytokines and inhibiting osteoclastogenesis by its ROS adsorption.Moreover,local injection of FNC attenuates the UHMWPE-induced osteolysis in a mouse calvarial model.In sum,our results suggest that FNC can be used for treating osteolytic bone disease caused by excessive osteoclastogenesis.展开更多
Periprosthetic osteolysis(PPO)remains the key factor in implant failure and subsequent revision surgery and is mainly triggered by wear particles.Previous studies have shown that inhibition of osteoblastic differentia...Periprosthetic osteolysis(PPO)remains the key factor in implant failure and subsequent revision surgery and is mainly triggered by wear particles.Previous studies have shown that inhibition of osteoblastic differentiation is the most widespread incident affecting the interface of trabecular and loosening prostheses.Additionally,the NLRP3 inflammasome is activated by prosthetic particles.Sirtuin3,an NAD+-dependent deacetylase of mitochondria,regulates the function of mitochondria in diverse activities.However,whether SIRT3 can mitigate wear debris-induced osteolysis by inhibiting the NLRP3 inflammasome and enhancing osteogenesis has not been previously reported.Therefore,we investigated the role of SIRT3 during the process of titanium(Ti)particle-induced osteolysis.We revealed that upregulated SIRT3 dramatically attenuated Ti particle-induced osteogenic inhibition through suppression of the NLRP3 inflammasome and improvement of osteogenesis in vivo and in vitro.Moreover,we found that SIRT3 interference in the process of Ti particle-induced osteolysis relied on the GSK-3β/β-catenin signalling pathway.Collectively,these findings indicated that SIRT3 may serve as a rational new treatment against debris-induced PPO by deacetylase-dependent inflammasome attenuation.展开更多
基金supported by National Key R&D Program of China(2018YFC1105904,2016YFA0201104)National Science Foundation of China(81772335,81941009,81802196,11874200)+2 种基金Natural Science Foundation of Jiangsu Province,China(BK20180127)Jiangsu Provincial Key Medical Talent FoundationSix Talent Peaks Project of Jiangsu Province(WSW-079).
文摘Joint replacement surgery is one of the orthopedic surgeries with high successful rates;however,wear debris generated from prostheses can ultimately lead to periprosthetic osteolysis and failure of the implant.The implant-derived particulate debris such as ultrahigh molecular weight polyethylene(UHMWPE)can initiate the local immune response and recruit monocytic cells to phagocytose particles for generating reactive oxygen species(ROS).ROS induces osteoclastogenesis and macrophages to secrete cytokines which ultimately promote the development of osteolysis.In this work,we develop the few-layered Nb_(2)C(FNC)as an antioxidant which possesses the feature of decreasing the production of cytokines and inhibiting osteoclastogenesis by its ROS adsorption.Moreover,local injection of FNC attenuates the UHMWPE-induced osteolysis in a mouse calvarial model.In sum,our results suggest that FNC can be used for treating osteolytic bone disease caused by excessive osteoclastogenesis.
基金This work is supported by grants from the National Natural Science Foundation of China(Nos.82072425,82072498,81873991,81873990,81672238 and 81472077)the Young Medical Talents of Jiangsu Province(No.QNRC2016751)+1 种基金the Natural Science Foundation of Jiangsu Province(Nos.BK20180001)the Priority Academic Program Development of Jiangsu Higher Education Institutions and Special Project of Diagnosis and Treatment Technology for Key Clinical Diseases in Suzhou(LCZX202003).
文摘Periprosthetic osteolysis(PPO)remains the key factor in implant failure and subsequent revision surgery and is mainly triggered by wear particles.Previous studies have shown that inhibition of osteoblastic differentiation is the most widespread incident affecting the interface of trabecular and loosening prostheses.Additionally,the NLRP3 inflammasome is activated by prosthetic particles.Sirtuin3,an NAD+-dependent deacetylase of mitochondria,regulates the function of mitochondria in diverse activities.However,whether SIRT3 can mitigate wear debris-induced osteolysis by inhibiting the NLRP3 inflammasome and enhancing osteogenesis has not been previously reported.Therefore,we investigated the role of SIRT3 during the process of titanium(Ti)particle-induced osteolysis.We revealed that upregulated SIRT3 dramatically attenuated Ti particle-induced osteogenic inhibition through suppression of the NLRP3 inflammasome and improvement of osteogenesis in vivo and in vitro.Moreover,we found that SIRT3 interference in the process of Ti particle-induced osteolysis relied on the GSK-3β/β-catenin signalling pathway.Collectively,these findings indicated that SIRT3 may serve as a rational new treatment against debris-induced PPO by deacetylase-dependent inflammasome attenuation.
