The Natural Polyphenol Epigallocatechin Gallate Protects Intervertebral Disc Cells from Oxidative Stress.
Oxidative stress-related phenotypic changes and a decline in the number of viable cells are crucial contributors to intervertebral disc degeneration. The polyphenol epigallocatechin 3-gallate (EGCG) can interfere with painful disc degeneration by reducing inflammation, catabolism, and pain. In this study, we hypothesized that EGCG furthermore protects against senescence and/or cell death, induced by oxidative stress. Sublethal and lethal oxidative stress were induced in primary human intervertebral disc cells with H2O2 (total n = 36). Under sublethal conditions, the effects of EGCG on p53-p21 activation, proliferative capacity, and accumulation of senescence-associated β-galactosidase were tested. Further, the effects of EGCG on mitochondria depolarization and cell viability were analyzed in lethal oxidative stress. The inhibitor LY249002 was applied to investigate the PI3K/Akt pathway. EGCG inhibited accumulation of senescence-associated β-galactosidase but did not affect the loss of proliferative capacity, suggesting that EGCG did not fully neutralize exogenous radicals. Furthermore, EGCG increased the survival of IVD cells in lethal oxidative stress via activation of prosurvival PI3K/Akt and protection of mitochondria. We demonstrated that EGCG not only inhibits inflammation but also can enhance the survival of disc cells in oxidative stress, which makes it a suitable candidate for the development of novel therapies targeting disc degeneration.
Department of Health Sciences and Technology, Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093 Zurich, Switzerland.
Olga
O
Krupkova
Department of Health Sciences and Technology, Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093 Zurich, Switzerland; Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan.
Junichi
J
Handa
Department of Health Sciences and Technology, Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093 Zurich, Switzerland.
Marian
M
Hlavna
Prodorso, Walchestrasse 15, 8006 Zurich, Switzerland.
Juergen
J
Klasen
Department of Rheumatology, University Hospital, Zurich, Switzerland.
Caroline
C
Ospelt
Department of Health Sciences and Technology, Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093 Zurich, Switzerland.
Stephen John
SJ
Ferguson
Department of Health Sciences and Technology, Institute for Biomechanics, ETH Zurich, Hoenggerbergring 64, 8093 Zurich, Switzerland.
Karin
K
Wuertz-Kozak
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007403:Intervertebral Disc / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008875:Middle Aged; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015203:Reproducibility of Results; D055815:Young Adult; D001616:beta-Galactosidase / Q000378:metabolism
D000975:Antioxidants; D020011:Protective Agents; D017382:Reactive Oxygen Species; D002392:Catechin; C045651:epigallocatechin gallate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D001616:beta-Galactosidase