Methylmalonic Acid, an Aging-Associated Metabolite, Accelerates Intervertebral Disc Degeneration by Inducing Disc Vascularization via the CCL7/JAK2-STAT3/VEGF Signaling Axis - PubMed
4 days ago
- #aging
- #disc vascularization
- #VEGF
- Methylmalonic acid (MMA) levels are significantly elevated in intervertebral discs (IVDs) of elderly individuals, suggesting its role in aging-induced intervertebral disc degeneration (IVDD).
- MMA treatment in nucleus pulposus cells (NPCs) leads to upregulation of catabolic markers and downregulation of anabolic markers, accelerating IVDD progression.
- MMA upregulates CCL7 expression in NPCs, enhancing JAK2/STAT3 signaling and increasing vascular endothelial growth factor (VEGF) expression, promoting disc vascularization.
- Disc vascularization is identified as a key factor in IVDD progression, with VEGF as a potential therapeutic target.
- Lenvatinib, a VEGF receptor inhibitor, was shown to delay IVDD progression in rescue experiments.