College of Laboratory Medicine, Dalian Medical University, 9 Lushunnan Road Xiduan, Dalian, Liaoning Province, 116044, China.
Department of Sports Medicine, Dalian Municipal Central Hospital, Dalian, Liaoning Province, 116033, China.
Inflammation. 2018 Jun;41(3):959-971. doi: 10.1007/s10753-018-0750-6.
Osteoarthritis (OA), the most prevalent chronic and degenerative joint disease, is characterized by articular cartilage degradation and chondrocyte injury. Increased cell apoptosis and defective cell autophagy in chondrocytes are a feature of degenerative cartilage. MicroRNAs (miRNAs) have been identified as potential regulators of OA. This study aimed to determine the potential role of miR-140-5p and miR-149 in apoptosis, autophagy, and proliferation in human primary chondrocytes and investigate the underlying mechanism. We revealed the differential expressional profiles of miR-140-5p/149 and fucosyltransferase 1 (FUT1) in the articular cartilage tissues of OA patients and normal people and validated FUT1 was a direct target of miR-140-5p/149. The overexpression of miR-140-5p/149 inhibited apoptosis and promoted proliferation and autophagy of human primary chondrocytes via downregulating FUT1. On the contrary, the downregulation of miR-140-5p/149 inhibited chondrocyte proliferation and autophagy, whereas the effect was reversed by FUT1 knockdown. Taken together, our data suggested that miR-140-5p and miR-149 could mediate the development of OA, which was regulated by FUT1. miR-140-5p/miR-149/FUT1 axis might serve as a predictive biomarker and a potential therapeutic target in OA treatment.
骨关节炎(OA)是最常见的慢性退行性关节疾病,其特征为关节软骨降解和软骨细胞损伤。软骨细胞中细胞凋亡增加和细胞自噬缺陷是退行性软骨的特征。MicroRNAs(miRNAs)已被鉴定为 OA 的潜在调节剂。本研究旨在确定 miR-140-5p 和 miR-149 在人原代软骨细胞中的凋亡、自噬和增殖中的潜在作用,并探讨其潜在机制。我们揭示了 miR-140-5p/149 和岩藻糖基转移酶 1(FUT1)在 OA 患者和正常人关节软骨组织中的差异表达谱,并验证了 FUT1 是 miR-140-5p/149 的直接靶标。miR-140-5p/149 的过表达通过下调 FUT1 抑制人原代软骨细胞的凋亡,促进增殖和自噬。相反,miR-140-5p/149 的下调抑制软骨细胞的增殖和自噬,但通过 FUT1 敲低可逆转该作用。总之,我们的数据表明,miR-140-5p 和 miR-149 可以通过 FUT1 调节介导 OA 的发生。miR-140-5p/miR-149/FUT1 轴可能作为 OA 治疗的预测生物标志物和潜在治疗靶点。