Role of the tumor necrosis factor-alpha, cyclooxygenase-2, prostaglandin E2, and effect of low-intensity pulsed ultrasound in an in vitro herniated disc resorption model.
Spontaneous herniated disc resorption occurs via inflammatory reactions involving abundant neovascularization and macrophage phagocytotic activity. Nonthermal low-intensity pulsed ultrasound (LIPUS) treatment might be effective in shortening the duration of disc resorption. We developed a rat in vitro resorption model in which a coccygeal intervertebral disc and peritoneal macrophages were cocultured. Secretion of tumor necrosis factor-alpha (TNF-alpha) from macrophages was promoted by LIPUS, and the process of disc degeneration was thus accelerated. In this study, we further examined the effects of LIPUS using this in vitro model focusing on whether LIPUS affects cyclooxygenase-2 (COX-2) signaling pathways. We found that the levels of COX-2 and prostaglandin E2 (PGE2) secreted from macrophages were increased by LIPUS. However, these phenomena were not caused by LIPUS directly, as the levels of these substances were reduced by neutralizing TNF-alpha activity. Moreover, the wet weights of the disc samples were not changed by addition of PGE2, but were reduced by recombinant TNF-alpha. Our results suggest that the effects of LIPUS in enhancing the process of herniated disc resorption are caused mainly by TNF-alpha.
Iwabuchi
Sadahiro
S
Biomedical Engineering Laboratories, Teijin Pharma Ltd., 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan. iwabuchi@ist.hokudai. ac.jp
Ito
Masaya
M
Chikanishi
Toshihiro
T
Azuma
Yoshiaki
Y
Haro
Hirotaka
H
D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007405:Intervertebral Disc Displacement / Q000000981:diagnostic imaging* / Q000276:immunology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014463:Ultrasonography / Q000379:methods; D014945:Wound Healing / Q000276:immunology
D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D015232:Dinoprostone