Effect of Transforming Growth Factor Beta (TGF-β) on the Degeneration of Intervertebral Discs by Regulating Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells/Mammalian Target of Rapamycin (NF-fcB/mTOR) Signaling Pathway

Abstract

Intervertebral disc degenerative disease (IDDD) is common in orthopedics. TGF-β involves in inflammation and tissue repair. But its role in IDDD remains unclear. IDDD patients and normal intervertebral disc nucleus pulposus tissues were collected. IDDD was divided into prominent group and prolapse group. IDDD nucleus pulposus cells were isolated and divided into control group, TGF-β agonist group and TGF-β inhibitor group followed by analysis of cell proliferation by MTT, cell apoptosis by flow cytometry BALP and OC expression by Real time PCR, NF-/<B/mTOR signaling protein expression by Western blot as well as IL-1 and IL-6 secretion by ELISA. Compared with normal group, TGF-β mRNA and serum level in patients with IDDD was significantly decreased (P < 0.05), with more significant changes in prolapse group (P < 0.01). Pfirrmann grading scores were negatively correlated with TGF-β serum level (P < 0.001). TGF-β agonists can significantly promote cell proliferation, inhibit apoptosis, upregulate BALP and OC expression, inhibit NF-κB expression, increased p-mTOR level and decrease IL-1 and IL-6 secretion (P < 0.05). All these changes were significantly reversed by TGF-β inhibitors (P < 0.05). TGF-β expression in IDDD is reduced and associated with disease severity. Promoting TGF-β expression can inhibit inflammatory factors secretion, promote BALP and OC expression and cell proliferation, and inhibit the degeneration of intervertebral discs by regulating NF-/<B/mTOR signaling.