miR-9-5p通过抑制SIRT1调控骨关节炎发病进程中软骨细胞的凋亡  

miR-9-5p regulates chondrocyte apoptosis in osteoarthritis pathogenesis by inhibiting SIRT1

作　　者：王静[1] 马莎[1] 俞娟[1] 左大辰 殷子婧 李发有[1] 何霞 彭海婷 石晓庆 黄玮娟 李芹[1] WANG Jing;MA Sha;YU Juan;ZUO Da-chen;YIN Zi-jing;LI Fa-you;HE Xia;PENG Hai-ting;SHI Xiao-qing;HUANG Wei-juan;LI Qin(Department of Rheumatology,the First People's Hospital of Yunnan Province,the Affiliated Hospital of Kunming University of Science and Technology,Kunming 650032,China)

机构地区：[1]云南省第一人民医院,昆明理工大学附属医院风湿免疫科,昆明650032

出　　处：《现代免疫学》2023年第3期197-205,210,共10页Current Immunology

基　　金：国家自然科学基金(81760407);昆医联合专项[2018FE001(-179)]。

摘　　要：为研究miR-9-5p靶向沉默信息调节因子2相关酶1(silent information regulator factor 2-related enzyme 1, SIRT1)对骨关节炎(osteoarthritis, OA)软骨细胞凋亡的影响及相关机制,对小鼠的原代软骨细胞进行分离、培养并构建OA细胞模型(加入IL-1β)和OA小鼠模型,检测miR-9-5p的表达、Caspase-3活性、细胞活性及凋亡。确定miR-9-5p和SIRT1存在靶向关系后检测SIRT1活性和上述指标。用番红O-固绿对OA小鼠组织进行染色并分析,在OA小鼠模型中再次验证miR-9-5p通过抑制SIRT1对软骨细胞凋亡的影响。结果显示,miR-9-5p mRNA在OA组织及IL-1β处理的软骨细胞中表达显著升高(P<0.001), miR-9-5p可抑制OA软骨细胞活性(P<0.001)并促进其凋亡(P<0.01)。miR-9-5p靶向作用于SIRT1,并通过抑制SIRT1抑制OA软骨细胞活性(P<0.001),促进其凋亡(P<0.05)。在OA动物模型的验证中得到相同的结果。该研究提示,miR-9-5p可通过靶向SIRT1抑制OA软骨细胞活性,促进OA软骨细胞凋亡,参与OA的发生和发展。This study aims to verify the regulation of miR-9-5p on the chondrocyte apoptosis by targeting the silent information regulator factor 2-related enzyme 1(SIRT1)in osteoarthritis(OA)and explore the related mechanisms.Primary chondrocytes from mice were isolated and cultured,and the cellular OA model was established by IL-1β-induction.An OA mouse model was also established.Subsequently,the expression of miR-9-5p,Caspase-3 activity,cell activity,and apoptosis in each group were detected.SIRT1 activity and the above indicators were detected after the targeting of miR-9-5p to SIRT1 was confirmed.The tissue samples of OA mice were stained and analyzed by safranine O-fast green,and the effect of miR-9-5p on chondrocyte apoptosis by inhibiting SIRT1 was verified again in the OA mouse model.The results showed that the expression of miR-9-5p mRNA was significantly increased in OA tissues and IL-1βtreated chondrocytes(P<0.001).miR-9-5p inhibited the activity of OA chondrocytes(P<0.001)and promoted apoptosis(P<0.01).miR-9-5p targeted SIRT1 and inhibited the activity of OA chondrocytes(P<0.001)and promoted their apoptosis by inhibiting SIRT1(P<0.05).The in vitro results were verified in the OA animal model.The study suggests that miR-9-5p may inhibit the activity of OA chondrocytes by targeting SIRT1 and promote the apoptosis of OA chondrocytes to regulate the occurrence and development of OA.

关 键 词：骨关节炎 微小RNA-9-5p 沉默信息调节因子2相关酶1 软骨细胞 凋亡 

分 类 号：R684.3[医药卫生—骨科学]