Fig. 3

Role of macrophages in endplate degeneration. a Classification and MRI characteristics of Modic changes. MC1 (low T1 and high T2 signals) is associated with edema and inflammation. MC2 (high T1 and T2 signals) indicates a progression to fatty involution. MC3 (low T1 and T2 signals) signify vertebral endplate bone sclerosis. b Macrophages participate in MCs. In non-bacterial MCs, macrophages accelerate endplate degeneration by promoting the expressions of pro-inflammatory cytokines, MMPs, and ADAMTs. In bacterial MCs, a wider variety of tissue-derived macrophages, including peripheral blood macrophages and osteal macrophages, contribute to endplate inflammation, leading to more severe endplate degeneration. c Schematic of a healthy endplate microenvironment. CEPCs synthesize an extracellular matrix primarily composed of collagen II and ACAN. CEPSCs are stem cells for intrinsic repair of the endplate. d Schematic of endplate lesions. Endplate lesions includes calcification, erosion, fractures, and Schmorl’s nodes. e Macrophages promote endplate calcification. Macrophages enhance CASR expression in CEPCs and regulate carbohydrate metabolism to increase AGEs expression by releasing pro-inflammatory cytokines, thereby promoting calcification. Additionally, macrophages promote calcification by increasing ROS production, which induces osteogenic differentiation of CEPSCs. f Macrophages in endplate regeneration. Macrophages promote neovascularization of the endplate by releasing VEGF. Macrophages participate in bone remodeling by regulating osteoclast formation and bone resorption activity