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Spermidine promotes nucleus pulposus autophagy as a protective mechanism against apoptosis and ameliorates disc degeneration.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2018 Jun; Vol. 22 (6), pp. 3086-3096. Date of Electronic Publication: 2018 Mar 25. - Publication Year :
- 2018
-
Abstract
- Spermidine has therapeutic effects in many diseases including as heart diastolic function, myopathic defects and neurodegenerative disorders via autophagy activation. Autophagy has been found to mitigate cell apoptosis in intervertebral disc degeneration (IDD). Accordingly, we theorize that spermidine may have beneficial effects on IDD via autophagy stimulation. In this study, spermidine's effect on IDD was evaluated in tert-butyl hydroperoxide (TBHP)-treated nucleus pulposus cells of SD rats in vitro as well as in a puncture-induced rat IDD model. We found that autophagy was actuated by spermidine in nucleus pulposus cells. In addition, spermidine treatment weakened the apoptotic effects of TBHP in nucleus pulposus cells. Spermidine increased the expression of anabolic proteins including Collagen-II and aggrecan and decreased the expression of catabolic proteins including MMP13 and Adamts-5. Additionally, autophagy blockade using 3-MA reversed the beneficial impact of spermidine against nucleus pulposus cell apoptosis. Autophagy was thus important for spermidine's therapeutic effect on IDD. Spermidine-treated rats had an accentuated T2-weighted signal and a diminished histological degenerative grade than vehicle-treated rats, showing that spermidine inhibited intervertebral disc degeneration in vivo. Thus, spermidine protects nucleus pulposus cells against apoptosis through autophagy activation and improves disc, which may be beneficial for the treatment of IDD.<br /> (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
- Subjects :
- Animals
Apoptosis drug effects
Autophagy drug effects
Disease Models, Animal
Extracellular Matrix drug effects
Humans
Intervertebral Disc pathology
Intervertebral Disc Degeneration chemically induced
Intervertebral Disc Degeneration physiopathology
Nucleus Pulposus pathology
Primary Cell Culture
Rats
tert-Butylhydroperoxide toxicity
Intervertebral Disc drug effects
Intervertebral Disc Degeneration drug therapy
Nucleus Pulposus drug effects
Spermidine administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 22
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 29575654
- Full Text :
- https://doi.org/10.1111/jcmm.13586