Beneficial effects of hyperbaric oxygen on human degenerated intervertebral disk cells via suppression of IL-1β and p38 MAPK signal.
Nucleus pulposus cells (NPCs) from degenerating disks produce catabolic and inflammatory factors, including interleukin (IL)-1, nitric oxide (NO), prostaglandin E2 (PGE-2), and matrix metalloproteinaes (MMPs). An imbalance between MMPs and tissue inhibitors of matrix metalloproteinases (TIMPs) has been proposed to exist in the degenerating disk. This study evaluates the effects of hyperbaric oxygen (HBO) on the human degenerated NPCs. NPCs were maintained in alginate bead culture. All hyperoxic cells were exposed to 100% O(2) at 2.5 atmospheres absolute (ATA) in a hyperbaric chamber. p38 MAPK phosphorylation of the NPCs was detected using the phosphor-kinase array kit. RNA was isolated for real-time quantitative polymerase chain reaction (Q-PCR) analysis of aggrecan and type II collagen gene expression. The amounts of IL-1β, NO, PGE-2, MMP-3, and TIMP-1 in the conditioned media were quantified by enzyme-linked immunosorbent assay (ELISA). Our data showed that HBO treatment decreased expression of IL-1β, increased the gene expression of aggrecan and type II collagen, suppressed the phosphorylation of p38 MAPK, decreased NO, PGE-2, and MMP-3, and increased TIMP-1 expression in NPCs as compared with the atmospheric treatment. These results support the hypothesis that IL-1β and the p38 MAPK signal may be responsible for many of the inflammatory and catabolic changes seen in the human disk degeneration, and support our proposal that HBO treatment-induced increase of the anabolic factor (TIMP-1)/catabolic factor (MMP-3) ratio may provide a therapeutic approach to slow the course of intervertebral disk degeneration.
Niu
Chi-Chien
CC
Department of Orthopaedic Surgery and Hyperbaric Oxygen Therapy Center, Chang Gung Memorial Hospital, No 5, Fu-Hsing Street 333, Kweishan, Taoyuan, Taiwan.
Yuan
Li-Jen
LJ
Chen
Lih-Huei
LH
Lin
Song-Shu
SS
Tsai
Tsung-Ting
TT
Liao
Jen-Chung
JC
Lai
Po-Liang
PL
Chen
Wen-Jer
WJ
D053674:Aggrecans / Q000235:genetics; D002478:Cells, Cultured; D024043:Collagen Type II / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D006931:Hyperbaric Oxygenation; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000502:physiology; D055959:Intervertebral Disc Degeneration / Q000628:therapy*; D020935:MAP Kinase Signaling System; D019278:Matrix Metalloproteinase 3 / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology
D053674:Aggrecans; D024043:Collagen Type II; D053583:Interleukin-1beta; D019715:Tissue Inhibitor of Metalloproteinase-1; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; D015232:Dinoprostone