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Andrographolide influences IDD cell autophagy and oxidative stress under mechanical pressure via miR-9/FoxO3/PINK1/Parkin molecular axis.
- Source :
-
Cellular and molecular biology (Noisy-le-Grand, France) [Cell Mol Biol (Noisy-le-grand)] 2024 Jun 05; Vol. 70 (6), pp. 192-198. Date of Electronic Publication: 2024 Jun 05. - Publication Year :
- 2024
-
Abstract
- Intervertebral disc degeneration (IDD) is characterized by the decreased function and number of nucleus pulposus cells (NPCs) caused by excessive intervertebral disc (IVD) pressure. This research aims to provide novel insights into IDD prevention and treatment by clarifying the effect of andrographolide (ANDR) on IDD cell autophagy and oxidative stress under mechanical stress. Human primary NPCs were extracted from the nucleus pulposus tissue of non-IDD trauma patients. An IDD cell model was established by posing mechanical traction on NPCs. Through the construction of an IDD rat model, the influence of ANDR on IDD pathological changes was explored in vivo. The proliferation and autophagy of NPCs were decreased while the apoptosis rate and oxidative stress reaction were increased by mechanical traction. ANDR intervention obviously alleviated this situation. MiR-9 showed upregulated expression in IDD cell model, while FoxO3 and PINK1/Parkin were downregulated. Decreased proliferation and autophagy as well as enhanced apoptosis and oxidative stress response of NPCs were observed following miR-9 mimics and H89 intervention, while the opposite trend was observed after FoxO3 overexpression. FoxO3 is a direct target downstream miR-9. The in vivo experiments revealed that after ANDR intervention, the number of apoptotic cells in rat IVD tissue decreased and the autophagy increased. In conclusion, ANDR improves NPC proliferation, and autophagy, inhibits apoptosis and oxidative stress, and alleviates the pathological changes of IDD via the miR-9/FoxO3/PINK1/Parkin axis, which may be a new and effective treatment for IDD in the future.
- Subjects :
- Animals
Humans
Rats
Male
Apoptosis drug effects
Cell Proliferation drug effects
Signal Transduction drug effects
Female
Adult
Disease Models, Animal
MicroRNAs metabolism
MicroRNAs genetics
Autophagy drug effects
Forkhead Box Protein O3 metabolism
Forkhead Box Protein O3 genetics
Oxidative Stress drug effects
Intervertebral Disc Degeneration metabolism
Intervertebral Disc Degeneration pathology
Diterpenes pharmacology
Nucleus Pulposus metabolism
Nucleus Pulposus drug effects
Ubiquitin-Protein Ligases metabolism
Ubiquitin-Protein Ligases genetics
Protein Kinases metabolism
Protein Kinases genetics
Rats, Sprague-Dawley
Stress, Mechanical
Subjects
Details
- Language :
- English
- ISSN :
- 1165-158X
- Volume :
- 70
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cellular and molecular biology (Noisy-le-Grand, France)
- Publication Type :
- Academic Journal
- Accession number :
- 38836662
- Full Text :
- https://doi.org/10.14715/cmb/2024.70.6.29