Bone morphogenetic protein 9(BMP9)exhibits remarkable osteogenic potential.However,the intricate mechanisms driving this function of BMP9 remain elusive.This study en-deavors to investigate the potential role of sirtu...Bone morphogenetic protein 9(BMP9)exhibits remarkable osteogenic potential.However,the intricate mechanisms driving this function of BMP9 remain elusive.This study en-deavors to investigate the potential role of sirtuin 5(SIRT5)in enhancing BMP9’s osteogenic capacity and decipher the underlying molecular pathways.To achieve this aim,we employed real-time PCR,western blotting,histochemical staining,and a cranial defect repair model to assess the impact of SIRT5 on BMP9-mediated osteogenesis.We utilized real-time PCR,western blotting,immunofluorescent staining,and immunoprecipitation assay to explore the associated mechanisms.Our results revealed that SIRT5 significantly up-regulated BMP9-induced osteogenic markers,while SIRT5 knockdown reduced their expression.Concurrently,hypoxia-inducible factor 1 subunit alpha(HIF-1a)level was increased by SIRT5,but reduced by SIRT5 knockdown.Notably,HIF-1a potentiated the SIRT5’s ability to strengthen BMP9’s osteogenic potential,whereas HIF-1a silencing reduced this effect,which was confirmed by bone defect repair assay.The acetylation and malonylation levels of HIF-1a were reduced by SIRT5,which may enhance its stability to promote BMP9’s osteogenic effect.Conversely,SIRT5 knockdown reversed these effects and promoted the degradation of HIF-1a.Collectively,our results demonstrated that the BMP9’s osteogenic potential could be promoted by SIRT5,potentially through stabilizing HIF-1a by reducing its acetylation and malonylation modifica-tion.This discovery may offer a novel strategy to accelerate bone tissue engineering by enhancing osteogenic differentiation,and it also sheds light on the possible mechanisms un-derlying BMP9-mediated osteogenic differentiation.展开更多
基金supported by the Chongqing Medical University Program for Youth Innovation in Future Medicine(No.W0154 to B.C.H.and J.Y.L.)Chongqing Science and Technology Bureau(China)(No.CSTB2024NSCQ-MSX0411 to B.C.H.).
文摘Bone morphogenetic protein 9(BMP9)exhibits remarkable osteogenic potential.However,the intricate mechanisms driving this function of BMP9 remain elusive.This study en-deavors to investigate the potential role of sirtuin 5(SIRT5)in enhancing BMP9’s osteogenic capacity and decipher the underlying molecular pathways.To achieve this aim,we employed real-time PCR,western blotting,histochemical staining,and a cranial defect repair model to assess the impact of SIRT5 on BMP9-mediated osteogenesis.We utilized real-time PCR,western blotting,immunofluorescent staining,and immunoprecipitation assay to explore the associated mechanisms.Our results revealed that SIRT5 significantly up-regulated BMP9-induced osteogenic markers,while SIRT5 knockdown reduced their expression.Concurrently,hypoxia-inducible factor 1 subunit alpha(HIF-1a)level was increased by SIRT5,but reduced by SIRT5 knockdown.Notably,HIF-1a potentiated the SIRT5’s ability to strengthen BMP9’s osteogenic potential,whereas HIF-1a silencing reduced this effect,which was confirmed by bone defect repair assay.The acetylation and malonylation levels of HIF-1a were reduced by SIRT5,which may enhance its stability to promote BMP9’s osteogenic effect.Conversely,SIRT5 knockdown reversed these effects and promoted the degradation of HIF-1a.Collectively,our results demonstrated that the BMP9’s osteogenic potential could be promoted by SIRT5,potentially through stabilizing HIF-1a by reducing its acetylation and malonylation modifica-tion.This discovery may offer a novel strategy to accelerate bone tissue engineering by enhancing osteogenic differentiation,and it also sheds light on the possible mechanisms un-derlying BMP9-mediated osteogenic differentiation.
