Fig. 2

Role of macrophages in IVDD. a Macrophages amplify inflammation in the IVD. Macrophages upregulate the expression of pro-inflammatory cytokines, creating an inflammatory microenvironment and causing a series of effects on cellular activities and ECM metabolism. b Macrophage-related cytokines regulate PCDs of IVD cells, causing a significant loss of IVD cells. c Macrophages accelerate the senescence of IVD cells. d Macrophages regulate the proliferation of IVD cells. e Macrophages regulate ECM metabolism. Macrophages phagocytize disc fragments and regulate ECM metabolism by upregulating the expression of MMPs and ADAMTs. This activity can lead to the resorption of herinated NP or exacerbate the progression of IVDD. f Macrophages regulate discogenic LBP. Macrophages can promote nerve growth by upregulating NGF, increasing IVD sensitization, and causing discogenic LBP through inflammatory factors. Macrophages can also promote the formation of new blood vessels in the IVD by upregulating VEGF expression, bringing more immune cells and exacerbating the immune response