miR-17-5p Regulates Heterotopic Ossification by Targeting ANKH in Ankylosing Spondylitis

• Main Authors: Xiong Qin, Bo Zhu, Tongmeng Jiang, Jiachang Tan, Zhenjie Wu, Zhenchao Yuan, Li Zheng, Jinmin Zhao
• Format: Article
• Language: English
• Published: Elsevier 2019-12-01
• Series: Molecular Therapy: Nucleic Acids
• Online Access: http://www.sciencedirect.com/science/article/pii/S2162253119302793

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized with heterotopic ossification of the axis joints ligaments, resulting in joint disability. MicroRNAs (miRNAs) are regulators of mRNAs that play a crucial role in the AS pathological process. Here, we showed that the level of miR-17-5p was significantly higher in fibroblasts and ligament tissues from AS patients as compared to the non-AS individuals. Knockdown of the miR-17-5p from the fibroblasts derived from AS patients exhibited decreased osteogenic differentiation and ossification. On the other hand, AS patient-derived fibroblasts overexpressing miR-17-5p displayed the increased osteogenesis. Furthermore, inhibition of miR-17-5p ameliorated osteophyte formation, and the sacroiliitis phenotype in AS rats received emulsified collagen. Mechanistically, miR-17-5p regulated osteogenic differentiation by targeting the 3ʹ UTR of ankylosis protein homolog (ANKH). Also, downregulation of miR-17-5p slowed AS progression through regulation of cytokines, such as dickkopf-1 (DKK1) and vascular endothelial growth factor (VEGF). In conclusion, our findings reveal a role of the miR-17-5p-ANKH axis in the regulation of heterotopic ossification, which is essential for therapeutic intervention in heterotopic ossification in AS.