期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 20, 页码 -出版社
MDPI
DOI: 10.3390/ijms232012216
关键词
intervertebral disc degeneration; human nucleus pulposus; microglia; proinflammation; chemotaxis
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2019R1A6A3A01091920, 2020R1F1A1068910, 2022R1I1A1A01054001, 2022R1I1A1A01063094, 2020R1A2C2010285]
- National Research Foundation [I21SS7606036]
- National Research Foundation of Korea [2022R1I1A1A01063094, 2020R1F1A1068910, 2020R1A2C2010285, 2022R1I1A1A01054001, 2019R1A6A3A01091920] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
This study investigated the inflammatory response of microglial cells in a reconstituted degenerative intervertebral disc (IVD) model. The findings suggest that degenerative IVD may induce degenerative microglial proinflammation, leading to the development of low back pain (LBP).
Degeneration of the intervertebral disc (IVD) is a major contributor to low back pain (LBP). IVD degeneration is characterized by abnormal production of inflammatory cytokines secreted by IVD cells. Although the underlying molecular mechanisms of LBP have not been elucidated, increasing evidence suggests that LBP is associated particularly with microglia in IVD tissues and the peridiscal space, aggravating the cascade of degenerative events. In this study, we implemented our microfluidic chemotaxis platform to investigate microglial inflammation in response to our reconstituted degenerative IVD models. The IVD models were constructed by stimulating human nucleus pulposus (NP) cells with interleukin-1 beta and producing interleukin-6 (129.93 folds), interleukin-8 (18.31 folds), C-C motif chemokine ligand-2 (CCL-2) (6.12 folds), and CCL-5 (5.68 folds). We measured microglial chemotaxis (p < 0.05) toward the conditioned media of the IVD models. In addition, we observed considerable activation of neurodegenerative and deactivation of protective microglia via upregulated expression of CD11b (p < 0.001) and down-regulation of CD206 protein (p < 0.001) by soluble factors from IVD models. This, in turn, enhances the inflammatory milieu in IVD tissues, causing matrix degradation and cellular damage. Our findings indicate that degenerative IVD may induce degenerative microglial proinflammation, leading to LBP development.
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