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Hyperbaric oxygen treatment suppresses MAPK signaling and mitochondrial apoptotic pathway in degenerated human intervertebral disc cells
Author(s) -
Niu ChiChien,
Lin SongShu,
Yuan LiJen,
Chen LihHuei,
Wang IChun,
Tsai TsungTing,
Lai PoLiang,
Chen WenJer
Publication year - 2013
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22209
Subject(s) - p38 mitogen activated protein kinases , kinase , apoptosis , microbiology and biotechnology , mapk/erk pathway , aggrecan , signal transduction , protein kinase a , caspase , phosphorylation , chemistry , biology , biochemistry , programmed cell death , medicine , pathology , articular cartilage , alternative medicine , osteoarthritis
Nucleus pulposus cells (NPCs) from degenerating discs produce catabolic and inflammatory factors, including interleukin (IL)‐1 and nitric oxide (NO). Enhanced production of NO has been implicated in the apoptosis of degenerating disc cells. This study evaluates the effects of hyperbaric oxygen (HBO) on degenerated human NPCs. All hyperoxic cells were exposed to 100% O 2 at 2.5 atmospheres absolute (ATA). Phosphorylation of extracellular signal‐regulated kinase 1/2 (ERK1/2), c‐Jun N‐terminal kinase (JNK), and p38 mitogen‐activated protein kinase (MAPK) in NPCs was detected using the phosphor‐kinase array kit. RNA was isolated for real‐time polymerase chain reaction (PCR) analysis of aggrecan and type II collagen gene expression. The levels of IL‐1β and NO were quantified by enzyme‐linked immunosorbent assay (ELISA). To identify the HBO‐induced anti‐apoptotic pathways, expression of Bcl‐2 and Bax proteins as well as activation of cysteine‐containing aspartate‐specific proteases (caspases) 3, 8, and 9 was evaluated using Western blotting after HBO treatment. Our data showed that HBO treatment decreased the expression of IL‐1β, suppressed phosphorylation of ERK1/2, JNK, and p38 MAPK, decreased synthesis of NO, and increased the gene expression of aggrecan and type II collagen in NPCs as compared with the atmospheric treatment. HBO up‐regulated the ratio of Bcl‐2 to Bax expression and reduced the activity of caspases 9 and 3 but not of caspase 8, indicating a selective effect over the mitochondrial apoptosis pathway in degenerated NPCs. These results support our hypothesis that HBO treatment suppresses MAPK signaling and mitochondrial apoptotic pathway in degenerated human intervertebral disc cells. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 204–209, 2013