Abstract
Low back pain (LBP) 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. Recent work in musculoskeletal degenerative diseases such as 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, specifically, mast cell-IVD cell interactions using immunohistochemistry and 3D in-vitro cell culture methods. Mast cells were upregulated in painful human IVD tissue and induced an inflammatory, catabolic and pro-angiogenic phenotype in bovine nucleus pulposus and cartilage endplate cells at the gene level. Healthy bovine annulus fibrosus cells, however, demonstrated a protective role against key inflammatory (IL-1β and TNFα) 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 that characterize the degenerate IVD, making them a potential therapeutic target for LBP.
Highlights
Low back pain (LBP) is a debilitating disorder that affects nearly 80% of the population at least once in their lifetime, costing more than $100 billion in lost wages, decreased productivity, and medical costs in the US alone[1]
The cells within the healthy intervertebral disc (IVD), in particular the nucleus pulposus (NP), function to maintain a constant balance between catabolic and anabolic remodeling of the extracellular matrix (ECM), which is primarily composed of proteoglycans and collagens I/II
stem cell factor (SCF) staining in autopsy samples revealed a significant increase in expression within the NP (32.1%) region when compared to the annulus fibrosus (AF) region (9.3%) (p = 0.017) (Fig. 2B)
Summary
Low back pain (LBP) is a debilitating disorder that affects nearly 80% of the population at least once in their lifetime, costing more than $100 billion in lost wages, decreased productivity, and medical costs in the US alone[1]. Degeneration of the IVD is often associated with inflammation, immune cell infiltration and neo-vascularization – processes that occur during normal tissue healing; in the hostile microenvironment of the IVD these processes augment catabolism and pain rather than instigating repair[6]. While the healthy intervertebral disc is avascular and aneural, it is thought that degeneration induces structural and biochemical changes that contribute to angiogenesis and subsequent innervation of the disc, effectively sensitizing the IVD and resulting in low back pain[26]. This process is likely further perpetuated by the activity of immune cells that have infiltrated the disc. T lymphocytes have shown to be present in degenerative discs[31], causing an upregulation of IL-1732 and production of other important cytokines in IVD degeneration[33]; whereas the role of innate immune cells, i.e. mast cells is less well defined
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