miR-17-5p Regulates Heterotopic Ossification by Targeting ANKH in Ankylosing Spondylitis
| Autor: | Bo Zhu, Jinmin Zhao, Jiachang Tan, Xiong Qin, Zhenjie Wu, Tongmeng Jiang, Zhenchao Yuan, Li Zheng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
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 |
| Zdroj: | Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 18, Iss, Pp 696-707 (2019) |
| ISSN: | 2162-2531 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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