Macrophage-derived PDGF-BB modulates glycolytic enzymes expression and pyroptosis in nucleus pulposus cells via PDGFR-β/TXNIP pathway

Abstract

ObjectiveIntervertebral Disc Degeneration (IVDD) is one of the leading causes of low back pain, significantly impacting both individuals and society. This study aimed to investigate the significance of macrophage infiltration and the role of macrophage-secreted platelet-derived growth factor-BB (PDGF-BB) in IVDD progression. MethodsTo confirm the protective function of macrophage-derived PDGF-BB on nucleus pulposus cells (NPCs), we employed Lysm-Cre transgenic mice to genetically ablate PDGF-B within the myeloid cells. Immunohistochemistry was utilized to detect the expression of glycolytic enzymes and pyroptosis-related proteins during the process of IVDD. Western blot, RT-PCR, ELISA and immunofluorescence were used to detect the protective effect of recombinant PDGF-BB on NPCs. ResultsMacrophage-derived PDGF-BB deficiency resulted in the loss of NPCs and the increased ossification of cartilage endplates during lumbar disc degeneration. Also, PDGF-BB deficiency triggered the inhibition of glycolytic enzymes’ expression and the activation of pathways related to pyroptosis in nucleus pulposus. Mechanistically, our results suggest that PDGF-BB predominantly conveys its protective influence on NPCs through the PDGF receptor- beta (PDGFR-β)/ thioredoxin-interacting protein (TXNIP) pathway. ConclusionsThe absence of PDGF-BB originating from macrophages expedites the advancement of IVDD, whereas the application of PDGF-BB treatment holds potential for retarding intervertebral disc degeneration in the human body.