TNF and intervertebral disk degenerative disorder: During the process of IDD, HMGB1 is significantly upregulated in the intervertebral disc (IVD) and promotes the expression of inflammatory cytokines such as prostaglandin E2 (PGE2), TNF-α, IL-6, and IL-8 and matrix metalloproteinases (MMPs) (Rajan et al., 2013; Fang and Jiang, 2016).