Baek Dawoon, Lee Kyoung-Mi, Park Ki Won, Suh Jae Wan, Choi Seong Mi, Park Kwang Hwan, Lee Jin Woo, Kim Sung-Hwan
Department of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea.
Department of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea.
Mol Ther Nucleic Acids. 2018 Dec 7;13:322-333. doi: 10.1016/j.omtn.2018.09.015. Epub 2018 Sep 27.
Traumatic and degenerative lesions of articular cartilage usually progress to osteoarthritis (OA), a leading cause of disability in humans. MicroRNAs (miRNAs) can regulate the differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) and play important roles in the expression of genes related to OA. However, their functional roles in OA remain poorly understood. Here, we have examined miR-449a, which targets sirtuin 1 (SIRT1) and lymphoid enhancer-binding factor-1 (LEF-1), and observed its effects on damaged cartilage. The levels of chondrogenic markers and miR-449a target genes increased during chondrogenesis in anti-miR-449a-transfected hBMSCs. A locked nucleic acid (LNA)-anti-miR-449a increased cartilage regeneration and expression of type II collagen and aggrecan on the regenerated cartilage surface in acute defect and OA models. Furthermore, intra-articular injection of LNA-anti-miR-449a prevented disease progression in the OA model. Our study indicates that miR-449a may be a novel potential therapeutic target for age-related joint diseases like OA.
关节软骨的创伤性和退行性病变通常会发展为骨关节炎（OA），这是人类致残的主要原因。微小RNA（miRNA）可以调节人骨髓间充质干细胞（hBMSC）的分化，并在与OA相关的基因表达中发挥重要作用。然而，它们在OA中的功能作用仍知之甚少。在这里，我们研究了靶向沉默调节蛋白1（SIRT1）和淋巴样增强因子结合因子1（LEF-1）的miR-449a，并观察了其对受损软骨的影响。在转染抗miR-449a的hBMSC软骨生成过程中，软骨生成标志物和miR-449a靶基因的水平升高。在急性缺损和OA模型中，锁核酸（LNA）-抗miR-449a增加了软骨再生以及再生软骨表面II型胶原蛋白和聚集蛋白聚糖的表达。此外，关节内注射LNA-抗miR-449a可防止OA模型中的疾病进展。我们的研究表明，miR-449a可能是OA等与年龄相关的关节疾病的新型潜在治疗靶点。
