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MicroRNA-129-5p affects immune privilege and apoptosis of nucleus pulposus cells via regulating FADD in
Nan Li1, Qi Gao2,3, Wenli Zhou1
1Department of Neonatology, The First Hospital of Jilin University, Changchun, Jilin, China.
Abstract:
Literatures indicate that microRNA-129-5p (miR-129-5p) or Fas-associated death domain (FADD) is related to intervertebral disc degeneration (IDD), but the effect of miR-129-5p/FADD axis on IDD is not studied. The study aimed to investigate whether miR-129-5p influenced immune privilege and nucleus pulposus (NP) cell apoptosis in rats with IDD via regulating FADD.A rat model with caudal IDD was established, and injected with miR-129-5p agomir or miR-129-5p antagomir to figure out the character of miR-129-5p in the cell apoptosis and inflammation in the nucleus pulposus (NP) tissues of IDD rats. NP cells were grouped as the same ways for determining proliferation, apoptosis, and senescence in NP cells of IDD rats. Annexin V-FITC/PI double staining detected the apoptosis of macrophages and CD8+ cells co-cultured via transfected NP cells. Expression of miR-129-5p, FADD, collagen I, collagen II, aggrecan and Sox-9 in NP tissues and cells were determined.Up-regulated miR-129-5p decreased FADD, collagen I and elevated collagen Ⅱ, aggrecan, and Sox-9 in NP tissues and repressed inflammation in serum and NP tissues in IDD rats. Up-regulated miR-129-5p facilitated proliferation, inhibited senescence, apoptosis, and decreased FADD, collagen I and increased collagen Ⅱ, aggrecan, and Sox-9 in NP cells of IDD rats. Elevated miR-129-5p promoted the apoptosis of macrophages and CD8+ cells.We pronounced that up-regulated miR-129-5p inhibited the apoptosis and facilitated the proliferation of NP cells, as well as the apoptosis of macrophages and CD8+ cells via decreased FADD in IDD, suggesting that miR-129-5p had a protective effect on IDD.
Insights
MicroRNA-129-5p (miR-129-5p) protects against intervertebral disc degeneration (IDD) by reducing Fas-associated death domain (FADD) and inhibiting nucleus pulposus cell apoptosis.
Area of Science:
- Biomedical Science
- Molecular Biology
- Regenerative Medicine
Background:
- Intervertebral disc degeneration (IDD) is a significant cause of low back pain.
- The roles of microRNA-129-5p (miR-129-5p) and Fas-associated death domain (FADD) in IDD are not fully understood.
- Investigating the miR-129-5p/FADD axis is crucial for understanding IDD pathogenesis.
Purpose of the Study:
- To investigate the effect of miR-129-5p on immune privilege and nucleus pulposus (NP) cell apoptosis in a rat model of IDD.
- To determine if miR-129-5p regulates FADD expression in IDD.
- To explore the therapeutic potential of miR-129-5p in IDD.
Main Methods:
- Established a rat model of caudal IDD.
- Administered miR-129-5p agomir or antagomir to IDD rats.
- Assessed NP cell proliferation, apoptosis, and senescence.
- Quantified apoptosis in macrophages and CD8+ cells.
- Measured expression levels of miR-129-5p, FADD, collagen I, collagen II, aggrecan, and Sox-9.
Main Results:
- Up-regulated miR-129-5p decreased FADD and collagen I, while increasing collagen II, aggrecan, and Sox-9 in NP tissues and cells.
- miR-129-5p repressed inflammation in serum and NP tissues of IDD rats.
- Elevated miR-129-5p promoted NP cell proliferation and apoptosis of macrophages and CD8+ cells, while inhibiting NP cell senescence and apoptosis.
Conclusions:
- Up-regulated miR-129-5p exerts a protective effect on IDD by inhibiting NP cell apoptosis and promoting proliferation.
- The mechanism involves the downregulation of FADD.
- miR-129-5p also modulates immune responses by promoting macrophage and CD8+ cell apoptosis, suggesting its potential as a therapeutic target for IDD.
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