miR-10a-5p Promotes Chondrocyte Apoptosis in Osteoarthritis by Targeting HOXA1

• Published in: Molecular therapy. Nucleic acids Vol. 14; pp. 398 - 409
• Main Authors: Ma, Yan, Wu, Yizheng, Chen, Junxin, Huang, Kangmao, Ji, Bin, Chen, Zhijun, Wang, Qiang, Ma, Jianjun, Shen, Shuying, Zhang, Jianfeng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2019; Elsevier Limited; American Society of Gene & Cell Therapy; Elsevier
• Subjects: Anterior cruciate ligament; Apoptosis; Arthritis; Binding sites; Biotechnology; Cartilage (articular); Cartilage diseases; Cell growth; Chondrocytes; DNA nucleotidylexotransferase; Gene expression; Homeobox; homeobox protein HOXA1; HOXA1 protein; Hybridization; IL-1β; Immunoglobulins; Investigations; Joint diseases; microRNA; MicroRNAs; miR-10a-5p; miRNA; Osteoarthritis; Pathogenesis; Proteins; siRNA; Therapeutic applications; Transfection; United States > US; China; microRNA; apoptosis; miR-10a-5p; osteoarthritis; homeobox protein HOXA1
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2018.12.012

Osteoarthritis (OA) is a common joint disease characterized by degradation of the articular cartilage and joint inflammation. Studies have revealed the importance of microRNAs in the regulation of chondrocyte apoptosis. MicroRNA deep sequencing of control and osteoarthritic cartilage has revealed that miR-10a-5p is significantly upregulated in osteoarthritic tissues. However, its role in these tissues remains unknown. The present study was conducted to investigate the effect of miR-10a-5p in promoting OA. miR-10a-5p expression was increased in chondrocytes after interleukin-1β treatment in vitro. Transfection with a miR-10a-5p inhibitor abrogated interleukin-1β-induced apoptosis. A luciferase activity assay showed that miR-10a-5p targeted the 3′ UTR of the homeobox gene HOXA1, inhibiting its expression. Treatment with HOXA1 siRNA reversed the rescuing effect of the miR-10a-5p inhibitor on chondrocyte apoptosis. Additionally, an OA model was established in mice by anterior cruciate ligament transection. AntagomiR-10a-5p improved the cartilage surfaces of osteoarthritic mice, whereas agomiR-10a-5p worsened them. A terminal deoxynucleotidyl transferase dUTP nick-end labeling assay indicated reduced apoptosis and increased HOXA1 expression in osteoarthritic mice after miR-10a-5p knockdown. These findings reveal a novel mechanism regulating OA progression and demonstrate the potential of miR-10a-5p and homeobox protein HOXA1 as therapeutic targets.