Wen-Lung Liu

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.

Background: There are still debates on the long-term outcome of treating pathological thoracolumbar fractures, including osteoporosis and oncologic problems, using vertebroplasty. Methods: We collected 8625 patients with pathological thoracolumbar fractures (ICD-9-CM codes 733.13 combined with 805.2 or 805.4) between the years of 2003 to 2013, from the two million random samples from the National Health Insurance Research Database in Taiwan. Survival analysis was conducted to estimate the mortality risks of different treatments, including vertebroplasty (n = 1389), conventional open surgery (n = 1219), or conservative treatment (n = 6017). A multivariable Cox proportional hazard model was constructed for adjustment of age, gender, comorbidities and complications. Results: Crude incidence rate of patients with pathological thoracolumbar fractures in Taiwan gradually increased year by year. Compared with conservative treatment, conventional open surgery and vertebroplasty seemed to improve long-term survival with adjusted hazard ratios (aHR) of 0.80 (95% confidence interval (CI) 0.70–0.93), and 0.87 (95% CI 0.77–0.99), respectively. The survival advantage of vertebroplasty appeared more evident for those aged over 75. However, we were unable to rule out confounding by indication. Conclusion: Although conventional open surgery would usually be the best choice for the treatment of patients with pathological thoracolumbar fractures, database information from current real-world practice appears to support vertebroplasty as a viable choice for elderly people over 75 years of age.

Degenerative lumbar spondylolisthesis (DLS) is a major cause of spinal canal stenosis and is often related to lower back pain. IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory bone disorders likes intervertebral disc herniation, rheumatoid arthritis (RA), osteoporosis, and bone fracture. IL-19 also acts as a proinflammatory cytokine in RA. The aim of the present study was to investigate whether IL-19 and IL-20 are involved in DLS and compare three different tissues including disc, facet joint, and ligamentum flavum of patients with DLS to verify which tissue is affected more by inflammation. Disc, facet joint and ligamentum flavum from 13 patients with DLS was retrieved, and the expression pattern of IL-19, IL-20, IL-20R1, IL-20R2, TNF-α, IL-1β, and MCP-1 was evaluated using immunohistochemical staining with specific antibodies. The disc cells were isolated and incubated with IL-19 and IL-20 under CoCl2-mimicked hypoxic conditions to analyze the proinflammatory cytokine expression pattern using real-time quantitative PCR with specific primers. IL-19 and IL-20 were positively stained and accompanied by abundant expression of TNF-α, IL-1β, and MCP-1 in facet joints of DLS patients. IL-19 and IL-20’s receptors (IL-20R1 and IL-20R2) were expressed on chondrocytes and fibrocytes/fibroblasts in facet joint and ligamentum flavum tissues from patients with DLS. There was a significant correlation between the expression of IL-20 and IL-1β in facet joint. In vitro assay, IL-19 and IL-20 upregulated the expression of IL-1β, IL-6, TNF-α, IL-8, VEGF, and MCP-1 in primary cultured DLS disc cells under CoCl2-mimicked hypoxic conditions. IL-19, IL-20, and their receptors as well as proinflammatory cytokines (TNF-α, IL-1β, and MCP-1) were expressed more in facet joints than the other tissues in patients with DLS; therefore, the etiology of inflammation might be more facet-centric. IL-19 and IL-20 induced proinflammatory cytokine expression in disc cells and might play a role in the pathogenesis of DLS.