运动通过提高OGT依赖的O-GlcNAcylation促进骨生成  

Exercise promotes osteogenesis by increasing OGT-dependent O-GlcNAcylation

作　　者：赵青 夏燕 谢幸尔[1] ZHAO Qing;XIA Yan;XIE Xinger(Department of Orthopedics,The Third Affiliated Hospital of Nantong University,Nantong 226000,China)

机构地区：[1]南通大学附属南通第三医院,南通226000

出　　处：《生命的化学》2024年第11期2152-2159,共8页Chemistry of Life

基　　金：南通市基础科学研究项目(MSZ2022003)。

摘　　要：运动/机械应力可以有效促进骨生成,进而预防骨质疏松疾病的发生,但其作用机制尚不完全明确。O-连接β-N-乙酰氨基葡萄糖(O-linkedβ-N-acetylglucosamine,O-GlcNAc)糖基化修饰(O-GlcNAc glycosylation modification,O-GlcNAcylation)是一种蛋白质翻译后修饰,在多种疾病的发生发展进程中发挥重要调控作用。氧连氮-乙酰葡萄糖胺转移酶(O-GlcNAc transferase,OGT)是O-GLcNAc糖基化修饰的关键酶,已有的研究证明OGT可以促进成骨分化,但其是否参与运动/机械应力促进骨生成的过程,目前尚未见有研究报道。本研究采用生长期小鼠进行跑台运动干预,同时使用Flexcell系统对MC3T3-E1细胞进行机械牵张干预,以此探究运动/机械应力对骨或成骨细胞O-GLcNAc糖基化修饰(OLinked N-Acetylglucosamine,RL2)、OGT的影响。结果发现,跑台运动可以提高生长期小鼠的骨量和骨密度(bone mineral density,BMD),提高成骨分化标志物碱性磷酸酶(alkaline phosphatase,ALP)、runt相关转录因子2(runt-related transcription factor 2,Runx2)、激活转录因子4(activated transcription factor 4,ATF4)等在骨组织中的表达,同时提高骨组织的O-GLcNAc糖基化修饰水平和OGT的表达。MC3T3-E1细胞向成骨诱导分化7 d后,发现其ALP的活性显著增加,O-GLcNAc糖基化修饰水平和OGT的表达也显著增加。机械牵张干预可以促进成骨分化标志物ALP、Runx2、ATF4等的表达,同时提高O-GLcNAc糖基化修饰水平和OGT的表达。本研究结果提示,运动/机械应力可能通过提高OGT的表达来促进成骨分化和骨生成。Exercise/mechanical stress can be effective in promoting osteogenesis and thus preventing and combating osteoporotic diseases.However,the underlying mechanisms are not fully understood.O-linkedβ-N-acetylglucosamine(O-GlcNAc)glycosylation modification(O-GlcNAcylation)is a post-translational modification of proteins,which plays an important regulatory role in the developmental process of many diseases.O-GlcNAc transferase(OGT)is a key enzyme for O-GLcNAc modification.Although it has been demonstrated that OGT promotes osteogenic differentiation,whether OGT is involved in the process of exercise/mechanical stress promoting osteogenesis has not yet been reported.In this study,growth-phase mice were used for treadmill exercise intervention,while MC3T3-E1 cells were subjected to mechanical tension intervention by the Flexcell cellular tension system to investigate the effects of exercise/mechanical stress on O-Linked N-acetylglucosamine(RL2)and OGT in bone/osteoblasts.The results revealed that treadmill increased bone mass and bone mineral density(BMD),and increased the expression of osteogenic differentiation markers alkaline phosphatase(ALP),runt-related transcription factor 2(Runx2),and activated transcription factor 4(ATF4)in bone tissues of growing mice,as well as the level of RL2 and the expression of OGT in bone tissues.After 7 days of inducing MC3T3-E1 differentiation towards osteogenesis,a significant increase in ALP activity was found,as well as a significant increase in RL2 and OGT expression.Moreover,mechanical tension intervention promotes the expression of osteogenic differentiation markers ALP,Runx2,and ATF4,etc.,while increasing the expression of RL2 and OGT.The results of this study suggest that exercise/mechanical stress may promote osteogenic differentiation and osteogenesis by increasing OGT expression.

关 键 词：运动 机械应力 OGT 糖基化修饰 骨生成 

分 类 号：R580[医药卫生—内分泌]