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Molecular control of macrophages during intervertebral disc degeneration. (A). C-X-C and p38 MAPK signaling promote macrophage infiltration into the IVD during degeneration. (B). TNF-α and IFN-γ within the local microenvironment promote M1 polarization during IVD degeneration. (C). Inflammasome activation and HIF-1-α signaling influence nucleus pulposus cell apoptosis, and macrophage-produced MMPs and ADAMTSs promote ECM degradation within degenerated discs.
