| Popis: |
Low back pain is a widespread debilitating disorder of significant socio-economic importance and intervertebral disc (IVD) degeneration has been implicated in its pathogenesis. Despite its high prevalence the underlying causes of LBP and IVD degeneration are not well understood, contributing to the difficulty in identifying relevant treatment strategies that specifically target this disease. Recent work in musculoskeletal degenerative diseases such as rheumatoid arthritis and osteoarthritis have revealed a critical role for immune cells, specifically mast cells in their pathophysiology, eluding to a potential role for these cells in the pathogenesis of IVD degeneration. This study sought to characterize the presence and role of mast cells within the IVD, focusing on chemo-attractants (CCL2/MCP-1 and stem cell factor) which may recruitment mast cells to the IVD and mast cell-IVD cell interactions using immunohistochemistry and 3D in-vitro culture methods. Mast cells were upregulated in painful human intervertebral disc tissue and were able to induce an inflammatory, catabolic and pro-angiogenic phenotype in bovine nucleus pulposus and cartilage endplate cells at the gene level. Bovine annulus fibrosus cells in particular from the healthy IVD however, demonstrated a protective role against key inflammatory (IL-1ß and TNFa) and pro-angiogenic (VEGFA) genes expressed by mast cells, and mitigated neo-angiogenesis formation in vitro. In conclusion, mast cells can infiltrate and elicit a degenerate phenotype in IVD cells, enhancing key disease processes in the degenerate IVD and making them a potential target for low back pain therapeutics. |
