Abstract
Intervertebral disc (IVD) is an avascular tissue under hypoxic condition after adulthood. Our previous data showed that inflammatory cytokines (interleukin (IL)-1β), IL-20, and bone morphogenetic protein-2 (BMP-2) play important roles in the healing process after disc injury. In the current study, we investigated whether IL-1β, IL-20, or BMP-2 modulate the expression of pro-inflammatory cytokines, chemotaxis factor, and angiogenesis factor on IVD cells under hypoxia. IVD cells were isolated from patients with intervertebral disc herniation (HIVD) at the levels of L4–5 and L5–S1. We found that the expression of IL-1β, IL-20, BMP-2, hypoxia-inducible factor (HIF)-1α, IL-6, IL-8, angiogenetic factor (vascular endothelial growth factor (VEGF)), chemotactic factor (monocyte chemoattractant protein 1 (MCP-1)), and matrix metalloproteinase-3 (MMP-3) was upregulated in IVD cells under hypoxia conditions. In addition, IL-1β upregulated the expression of pro-inflammatory cytokines (IL-6 and IL-8), VEGF, MCP-1, and disc degradation factor (MMP-3) in IVD cells under hypoxia conditions. IL-20 upregulated MCP-1 and VEGF expression. BMP-2 also upregulated the expression of MCP-1, VEGF, and IL-8 in IVD cells under hypoxia conditions. Treatment with antibody against IL-1β decreased VEGF and MMP-3 expression, while treatment with IL-20 or BMP-2 antibodies decreased MCP-1, VEGF, and MMP-3 expression. Moreover, IL-1β modulated both the expression of IL-20 and BMP-2, but IL-20 only modulated BMP-2 either under a hypoxic or normoxic condition. Therefore, we concluded that the inflammation, chemotaxis, matrix degradation, and angiogenesis after disc herniation are influenced by the hypoxic condition and controlled by IL-1β, IL-20, and BMP-2.
Highlights
Low back pain and sciatica are the common symptoms in patients with intervertebral disc herniation (HIVD) and degeneration [1,2]
The injured disc degenerated worse in the rhBMP-2-treated group compared with the saline-treated control group, rhBMP-2 plays a critical role in the injury response of the Intervertebral disc (IVD) after an annular tear, and we found that angiogenesis and inflammation were prominently induced by bone morphogenetic protein-2 (BMP-2) after disc injury [19]
We concluded that the inflammation, chemotaxis, matrix degradation, and angiogenesis after disc herniation are influenced by the hypoxic condition and controlled by IL-1β, inflammatory cytokines-20 (IL-20), and Bone morphogenetic proteins (BMPs)-2
Summary
Low back pain and sciatica are the common symptoms in patients with intervertebral disc herniation (HIVD) and degeneration [1,2]. Intervertebral discs (IVDs) degeneration is an important cause of neck, back, and radicular pain [3]. When IVD is herniated, the protruded NP causes a mechanical compression to the nerve root, and leads to nerve–root hyperemia, edema, and sciatica. The exposed NP is misrecognized as a foreign substance and induces macrophage migration and accumulation into the epidural space, which activates an inflammatory response cascade that results in degradation and resorption of herniated disc material [6,7,9,10,11]. The molecular mechanism of the autoimmune reaction induced by the exposed NP after disc herniation is still unclear. Whether several key cytokines trigger inflammatory cascade and promote angiogenesis in the degenerative process of IVD is still unclear and needs to be clarified
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