PMID: 30076618
Abstract
Nuclear factor (NF)-κB p65 plays a key role in the development of intervertebral disc degeneration (IDD). Herein, we found that messenger RNA levels of human triggering receptor expressed on myeloid cells‐2 (TREM2) and NF‐κB p65 were upregulated and strongly positive correlated (r2 = 0.299, P = 0.0126) in nucleus pulposus (NP) tissues of patients with IDD. To investigate the role of TREM2 in the development of IDD and whether NF‐κB p65 was the underlying mechanism, whereby TREM2 played its role, we established TREM2‐siRNA–transfected human degenerative NP cells and TREM2‐overexpression vector–transfected human normal NP cells. Degeneration of human NP cells was assessed by measuring cell apoptosis, cell proliferation, and the secretion of tumor necrosis factor‐α, interleukin (IL)‐1β, and IL‐6. Protein levels of Bcl2, Bax, total NF‐κB p65 in whole cell lysates, cytoplasm NF‐κB p65, and nuclear NF‐κB p65 were determined to evaluate underlying mechanisms. Our data elucidated that TREM2 silencing was a therapy for human degenerative NP cells through inhibiting cell apoptosis, promoting cell proliferation, suppressing production of tumor necrosis factor‐α, IL 1β, and IL‐6, and the mechanisms included decreasing Bax while enhancing Bcl2, downregulating total NF‐κB p65, and retarding NF‐κB p65 nuclear translocation. On the contrary, upregulated TREM2 showed the opposite effects, accelerating the degeneration of human normal NP cells. Downregulating TREM2 and total NF‐κB p65 and inhibiting NF‐κB p65 nucleus translocation were also confirmed in NP tissue samples of four IDD rats. We concluded that TREM2 functioned as a promoter in the degeneration of human NP cells. Downregulating TREM2 may be a novel therapeutic strategy for human IDD.
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