Back to Search
Start Over
Rapamycin prevents the intervertebral disc degeneration via inhibiting differentiation and senescence of annulus fibrosus cells.
- Source :
-
Aging [Aging (Albany NY)] 2018 Jan 18; Vol. 10 (1), pp. 131-143. - Publication Year :
- 2018
-
Abstract
- The effects of bleomycin and rapamycin on cellular senescence and differentiation of rabbit annulus fibrosus stem cells (AFSCs) were investigated using a cell culture model. The results showed that bleomycin induced cellular senescence in AFSCs as evidenced by senescence-associated secretory phenotype. The morphology of AFSCs was changed from cobblestone-like cells to pancake-like cells. The senescence-associated β-galactosidase activity, the protein expression of P16 and P21, and inflammatory-related marker gene levels IL-1β, IL-6, and TNF-α were increased in bleomycin-treated AFSCs in a dose-dependent manner. Rapamycin treatment decreased the gene expression of MMP-3, MMP-13, IL-1β, IL-6, TNF-α, and protein levels of P16 and P21 in bleomycin-treated AFSCs. Furthermore, neither bleomycin nor rapamycin changed the ribosomal S6 protein level in AFSCs. However, the phosphorylation of the ribosomal S6 protein was increased in bleomycin-treated AFSCs and decreased in rapamycin-treated AFSCs. AFSCs differentiated into adipocytes, osteocytes, and chondrocytes when they were cultured with respective differentiation media. Rapamycin inhibited multi-differentiation potential of AFSCs in a concentration-dependent manner. Our findings demonstrated that mammalian target of rapamycin (mTOR) signaling affects cellular senescence, catabolic and inflammatory responses, and multi-differentiation potential, suggesting that potential treatment value of rapamycin for disc degenerative diseases, especially lower back pain.
- Subjects :
- Analysis of Variance
Animals
Annulus Fibrosus pathology
Bleomycin pharmacology
Blotting, Western
Disease Models, Animal
Gene Expression
Humans
Intervertebral Disc Degeneration prevention & control
Lumbar Vertebrae
Rabbits
Real-Time Polymerase Chain Reaction
Stem Cells pathology
Annulus Fibrosus drug effects
Cellular Senescence drug effects
Sirolimus pharmacology
Stem Cells drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1945-4589
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Aging
- Publication Type :
- Academic Journal
- Accession number :
- 29348392
- Full Text :
- https://doi.org/10.18632/aging.101364