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Photobiomodulation on human annulus fibrosus cells during the intervertebral disk degeneration: extracellular matrix-modifying enzymes

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Abstract

Destruction of extracellular matrix (ECM) leads to degeneration of the intervertebral disk (IVD), which is a major contributor to many spine disorders. IVD degeneration is induced by pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), which are secreted by immune cells, including macrophages and neutrophils. The cytokines modulate ECM-modifying enzymes such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human annulus fibrosus (AF) cells. The resulting imbalance in catabolic and anabolic enzymes can cause generalized back, neck, and low back pain (LBP). Photobiomodulation (PBM) is known to regulate inflammatory responses and wound healing. The aim of this study was to mimic the degenerative IVD microenvironment, and to investigate the effect of a variety of PBM conditions (wavelength: 635, 525, and 470 nm; energy density: 16, 32, and 64 J/cm2) on the production of ECM-modifying-enzymes by AF cells under degenerative conditions induced by macrophage-conditioned medium (MCM), which contains pro-inflammatory cytokines such as TNF-α and IL-β secreted by macrophage during the development of intervertebral disk inflammation. We showed that the MCM-stimulated AF cells express imbalanced ratios of TIMPs (TIMP-1 and TIMP-2) and MMPs (MMP-1 and MMP-3). PBM selectively modulated the production of ECM-modifying enzymes in AF cells. These results suggest that PBM can be a therapeutic tool for degenerative IVD disorders.

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Acknowledgments

The manuscript submitted does not contain information about medical device(s)/drug(s). No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript. This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI13C1501), and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2015R1A1A2056873). This work was approved by Korea University Guro Hospital Institutional Review Board.

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Authors and Affiliations

  1. Department of Medical Sciences, Graduate School of Medicine, Korea University, 80, Guro-dong, Guro-gu, Seoul, 152-703, South Korea

    Min Ho Hwang, Kyoung Soo Kim, Chang Min Yoo, Jae Hee Shin, Hyo Geun Nam, Jin Su Jeong & Hyuk Choi

  2. Department of Neurosurgery, Guro Hospital, College of Medicine, Korea University, Seoul, South Korea

    Joo Han Kim

  3. Department of Advanced Materials Science and Engineering, College of Engineering, Kangwon National University, Chuncheon, South Korea

    Kwang Ho Lee

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  1. Min Ho Hwang
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Correspondence to Hyuk Choi.

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This study was conducted with the approval of the institutional review board of Korea University Hospital (KUGH12202-001), and their written informed consent was obtained from the subjects.

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Hwang, M.H., Kim, K.S., Yoo, C.M. et al. Photobiomodulation on human annulus fibrosus cells during the intervertebral disk degeneration: extracellular matrix-modifying enzymes. Lasers Med Sci 31, 767–777 (2016). https://doi.org/10.1007/s10103-016-1923-x

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