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.
MeSH terms
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Adult
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Aged
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Animals
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Annulus Fibrosus / immunology
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Annulus Fibrosus / metabolism*
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Annulus Fibrosus / pathology
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Cattle
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Cell Communication / genetics
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Cell Communication / immunology
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Cell Line
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Chondrocytes / immunology
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Chondrocytes / metabolism*
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Chondrocytes / pathology
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Female
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Gene Expression Regulation
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Humans
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Interleukin-1beta / genetics
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Interleukin-1beta / immunology
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Intervertebral Disc Degeneration / genetics
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Intervertebral Disc Degeneration / immunology
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Intervertebral Disc Degeneration / metabolism*
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Intervertebral Disc Degeneration / pathology
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Low Back Pain / genetics
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Low Back Pain / immunology
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Low Back Pain / metabolism*
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Low Back Pain / pathology
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Male
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Mast Cells / immunology
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Mast Cells / metabolism*
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Mast Cells / pathology
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Middle Aged
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / immunology
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Neovascularization, Pathologic / metabolism*
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Neovascularization, Pathologic / pathology
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Nucleus Pulposus / immunology
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Nucleus Pulposus / metabolism*
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Nucleus Pulposus / pathology
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Primary Cell Culture
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Signal Transduction
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / immunology
Substances
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IL1B protein, human
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Interleukin-1beta
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Tumor Necrosis Factor-alpha
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VEGFA protein, human
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Vascular Endothelial Growth Factor A