HMGB1 and intervertebral disk degenerative disorder: In another study, Lu et al. demonstrated that overexpressing High Mobility Group Box 1 (HMGB1) in macrophages accelerates disc degeneration via NF-κB activation and MMP3 upregulation in NP cells, and that treatment with glycyrrhizin, an HMGB1 inhibitor, mitigated these effects [19].