1. miR-17-5p Regulates Heterotopic Ossification by Targeting ANKH in Ankylosing Spondylitis
- Author
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Bo Zhu, Jinmin Zhao, Jiachang Tan, Xiong Qin, Zhenjie Wu, Tongmeng Jiang, Zhenchao Yuan, and Li Zheng
- Subjects
0301 basic medicine ,Joint ligament ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,Drug Discovery ,medicine ,Ankylosing spondylitis ,Ossification ,business.industry ,lcsh:RM1-950 ,Sacroiliitis ,medicine.disease ,Vascular endothelial growth factor ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,chemistry ,DKK1 ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Heterotopic ossification ,medicine.symptom ,business - Abstract
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.
- Published
- 2019