Circulating microRNA let-7e is decreased in knee osteoarthritis, accompanied by elevated apoptosis and reduced autophagy
Circulating microRNA let-7e is decreased in knee osteoarthritis, accompanied by elevated apoptosis and reduced autophagy
复制标题
膝骨关节炎中循环 microRNA let-7e 减少，并伴有细胞凋亡增加和自噬减少
DOI：
10.3892/ijmm.2020.4534
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发表时间：
2020-05-01
影响因子：
5.4
通讯作者：
Shen, Jin-Ming
中科院分区：
文献类型：
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作者：
Feng, Lei;Feng, Chun;Shen, Jin-Ming
膝骨关节炎（KOA）是老年人腿部残疾的主要原因。最近，有报道称循环microRNA (miRNA) let-7e在KOA中的表达水平显著降低。本研究的目的是评估let-7e作为检测KOA的血清标志物的可行性，并探讨其参与的潜在机制。基于以往的研究和生物信息学分析，let-7e可能调节关节软骨细胞的凋亡和自噬。共招募10例KOA患者和10例创伤无KOA患者检测外周血let-7e水平。随后，建立KOA大鼠模型，检测软骨和血清中let-7e的水平，研究软骨中凋亡蛋白和自噬相关蛋白的表达，检测原代培养软骨细胞的凋亡和自噬活性。KOA患者外周血let-7e水平较对照组明显降低，这一结果在KOA大鼠外周血和软骨中得到证实。此外，KOA大鼠软骨中凋亡通路相关蛋白表达水平升高，凋亡活性增强。KOA大鼠关节软骨中自噬相关蛋白beclin 1和微管相关蛋白1轻链3 β (LC3B) II/LC3BI的表达较对照组降低，自噬减少。四苗散（SMS）恢复了let-7e的表达，逆转了细胞凋亡和自噬的变化。因此，本研究为循环let-7e可能是诊断和治疗KOA的潜在血清生物标志物提供了额外的证据。软骨组织的细胞凋亡水平升高和自噬水平下降与KOA有关，用SMS治疗可以逆转这些影响。
Knee osteoarthritis (KOA) is a major cause of leg disability in the elderly population. Recently, the expression levels of circulating microRNA (miRNA) let-7e have been reported to be significantly reduced in KOA. The aims of the present study were to assess the feasibility of let-7e as a serum marker for detecting KOA and to explore the underlying mechanisms of its involvement. Based on previous studies and bioinformatics analysis, let-7e may regulate apoptosis and autophagy of articular chondrocytes. A total of 10 patients with KOA and 10 patients with trauma without KOA were recruited to examine the levels of let-7e in peripheral blood. Subsequently, KOA rat models were established, and the levels of let-7e in the cartilage and serum were examined, the expression of apoptotic proteins and autophagy-related proteins in the cartilage were investigated, and apoptotic and autophagic activities of primary cultured chondrocytes were also detected. In patients with KOA, let-7e levels in the peripheral serum were significantly decreased compared with the control group, and this result was confirmed in the peripheral serum and cartilage of KOA rats. In addition, the expression levels of proteins involved in the apoptotic pathway were increased in the cartilage of KOA rats, and apoptotic activity was increased. The expression of autophagy-related proteins beclin 1 and microtubule associated protein 1 light chain 3 β (LC3B) II/LC3BI in the articular cartilage of KOA rats was lower compared with the controls, and autophagy was decreased. Si-Miao-San (SMS) treatment restored the expression of let-7e and reversed the changes in apoptosis and autophagy. Therefore, the present study provided additional evidence that circulating let-7e may be a potential serum biomarker for the diagnosis and treatment of KOA. Elevated apoptosis levels and decreased autophagy levels of cartilage tissue are involved in KOA, and treatment with SMS may reverse these effects.