Abstract
The etiology of intervertebral disc (IVD) degeneration accompanied by low back pain (LBP) is largely unknown, and there are no curative therapies. Painful IVD degeneration is associated with infiltrated macrophage-mediated inflammatory response of human nucleus pulposus (NP) cells. The present study aimed to address the hypothesis that pro-inflammatory cytokines derived from macrophages lead to the altered molecular phenotype of human NP cells and to investigate the effects of phototherapy (630, 525, 465 nm with 16, 32, 64 J/cm2) on pain-related cytokine interleukin (IL)-6 and chemokine IL-8 under inflammatory conditions in human NP cells. Human NP cells were treated with soluble factors derived from macrophages in an inflammatory microenvironment, similar to that found in degenerative IVD. Human NP cells were also treated with phototherapy (630, 525, 465 nm with 16, 32, 64 J/cm2), and their cytokine and chemokine levels were detected. The soluble factors caused modulated expression of IL-6, IL-8, and matrix metalloproteinases (MMPs) at the gene and protein levels, causing a shift toward matrix catabolism through the expression of MMPs and increased pain-related factors via preferential activation of the nuclear factor-kappa B (NF-κB) p50 protein. Importantly, phototherapy attenuated the protein and gene expression of pain-related factor IL-6 at all doses and wavelengths. Interestingly, phototherapy also modulated the protein and gene expression of IL-8, which is responsible for the anabolic response, at a wavelength of 465 nm at all doses, in human NP cells. These findings suggested that phototherapy, at an optimal dose and wavelength, might be a useful therapeutic tool to treat IVD degeneration.
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Abbreviations
- 2-ME:
-
2-mercaptoethanol
- AF:
-
annulus fibrosus
- ANOVA:
-
analysis of variance
- BSA:
-
bovine serum albumin
- DAPI:
-
4′, 6-diamidino-2-phenylindol
- DRG:
-
dorsal root ganglion
- ELISA:
-
enzyme linked immunosorbent assay
- EP:
-
endplate
- FBS:
-
fetal bovine serum
- HBSS:
-
Hank’s balanced salt solution
- IL:
-
interleukin
- InGaAIP:
-
indium gallium aluminum phosphide
- IVD:
-
intervertebral disc
- LBP:
-
low back pain
- LDH:
-
lactate dehydrogenase
- LED:
-
light-emitting diode
- MCM:
-
macrophage-conditioned medium
- MMPs:
-
matrix metalloproteinases
- NF-κB:
-
nuclear factor-kappa B
- NP:
-
nucleus pulposus
- NPM:
-
NP cells exposed to macrophages
- P/S:
-
penicillin/streptomycin
- PBS:
-
phosphate-buffered saline
- PMA:
-
phorbol myristate acetate
- qPCR:
-
quantitative real-time polymerase chain reaction
- TNF-α:
-
tumor necrosis factor-alpha
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This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1D1A1A09000962).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all participants.
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Min Ho Hwang and Hyeong Guk Son are co-first authors.
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Hwang, M.H., Son, H.G., Lee, J.W. et al. Phototherapy suppresses inflammation in human nucleus pulposus cells for intervertebral disc degeneration. Lasers Med Sci 33, 1055–1064 (2018). https://doi.org/10.1007/s10103-018-2470-4
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DOI: https://doi.org/10.1007/s10103-018-2470-4