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Published on: May 3, 2024
Macrophage-derived PDGF-BB modulates glycolytic enzymes expression and pyroptosis in nucleus pulposus cells via
Xiaohang Zheng1, Jianxin Qiu1, Jiajing Ye1
1Orthopedic Department, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, China; Enze Medical Research Center, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, China.
Objective:
Intervertebral 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.
Methods:
To 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.
Results:
Macrophage-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 the 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 pathway.
Conclusions:
The absence of PDGF-BB originating from macrophages expedites the advancement of IVDD, whereas the application of PDGF-BB treatment holds the potential for retarding intervertebral disc degeneration in the human body.
Insights
Macrophage-derived platelet-derived growth factor-BB (PDGF-BB) protects against intervertebral disc degeneration (IVDD). Its absence accelerates IVDD, while PDGF-BB treatment may offer therapeutic benefits for this common cause of low back pain.
Area of Science:
- Biomedical research
- Orthopedics
- Cell biology
Background:
- Intervertebral disc degeneration (IVDD) is a primary cause of low back pain.
- Macrophages and their secreted factors play a role in IVDD.
- Platelet-derived growth factor-BB (PDGF-BB) is implicated in cellular processes relevant to IVDD.
Purpose of the Study:
- To investigate the role of macrophage infiltration in IVDD.
- To determine the significance of macrophage-secreted PDGF-BB in IVDD progression.
- To elucidate the protective mechanisms of PDGF-BB on nucleus pulposus cells (NPCs).
Main Methods:
- Genetic ablation of PDGF-B in myeloid cells using Lysm-Cre mice.
- Immunohistochemistry to assess glycolytic enzymes and pyroptosis markers.
- Western blot, RT-PCR, ELISA, and immunofluorescence to evaluate PDGF-BB's effects on NPCs.
Main Results:
- Macrophage-derived PDGF-BB deficiency led to NPC loss and cartilage endplate ossification.
- PDGF-BB deficiency inhibited glycolytic enzymes and activated pyroptosis pathways in the nucleus pulposus.
- PDGF-BB exerts protective effects on NPCs via the PDGFR-β/TXNIP pathway.
Conclusions:
- Absence of macrophage-derived PDGF-BB accelerates IVDD.
- PDGF-BB treatment shows potential for mitigating intervertebral disc degeneration in humans.
