Molecular profile of major growth factors in lumbar intervertebral disc herniation: Correlation with patient clinical and epidemiological characteristics

Abstract

The involvement of growth factors (GFs) in the pathogenesis of lumbar intervertebral disc (ID) herniation and the spontaneous resorption of herniated ID fragments remains only partially elucidated. A simultaneous assessment of the transcript levels of numerous GFs and their association with clinical and epidemiological profiles of human ID herniation would provide valuable insight into the biology and clinical course of the disease. In the present study, we examined simultaneously the transcript levels of vascular endothelial growth factor (VEGF), transforming growth factor β1 (TGF‑β1), basic fibroblast growth factor 2 (bFGF2), platelet derived growth factor (PDGF) isoforms and receptors, epidermal growth factor (EGF) and insulin growth factor‑1 (IGF‑1) in herniated and control ID specimens and investigated their correlation with the clinicopathological profiles of patients suffering from symptomatic lumbar ID herniation. GF mRNA expression levels were determined by RT-qPCR in 63 surgical specimens from lumbar herniated discs and 10 control ID specimens. Multiple positive correlations were observed between the transcript levels of the GFs examined in the ID herniation group. VEGF mRNA expression was significantly increased in the protruding compared with the extruded discs. Intense and acute pain significantly upregulated the PDGF transcript levels. Significant negative correlations were observed between the patient body mass index and the transcript levels of VEGF and PDGF receptors. Our findings support the hypothesis of the involvement of GFs in the natural history of ID herniation. GFs synergistically act in herniated IDs. Increased VEGF expression possibly induces the neovascularization process in the earliest stages of ID herniation. PDGF‑C and ‑D play a role in the acute phase of radiculopathy in a metabolic response for tissue healing. A molecular effect, in addition to the biomechanical effect of obesity in the pathogenesis of ID herniation is also implied.

Figure 1.

Normalized transcript levels of: (A) PDGF-C and (B) PDGF-D in regard to the duration of patient symptoms. PDGF, platelet derived growth factor.

Figure 2.

Normalized transcript levels of: (A) PDGF-B; (B) PDGF-C and (C) PDGF-D in regard to the intensity of pain experienced by the patients. PDGF, platelet derived growth factor; VAS, visual analogue scale.

Figure 3.

Normalized transcript levels of VEGF in regard to the type of ID herniation. ID herniation samples with protrusion exhibited an increased mRNA expression of VEGF compared with extruded discs (P=0.019, Mann-Whitney test). VEGF, vascular endothelial growth factor; ID, intervertebral disc.