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miR-17-5p Regulates Heterotopic Ossification by Targeting ANKH in Ankylosing Spondylitis
- Source :
- Molecular Therapy. Nucleic Acids, Molecular Therapy: Nucleic Acids, Vol 18, Iss, Pp 696-707 (2019)
- Publication Year :
- 2019
- Publisher :
- American Society of Gene & Cell Therapy, 2019.
-
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 3สน 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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 21622531
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy. Nucleic Acids
- Accession number :
- edsair.doi.dedup.....c6b6c8676e991b8a16201b2dac3f9f92