Intervertebral discs : metabolic responses to load, injury, and pro-inflammatory stimulation
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Introduction: Intervertebral disc (IVD) degeneration is a significant cause of back pain and disability. Factors such as trauma and magnitude and frequency of loading are associated with IVD degeneration. However, the contributions of mechanical loading, injury, pro-inflammatory stimulation, or any/all of these factors combined, are not fully known. Excessive/abnormal loading is thought to contribute to degeneration through disruption of the extracellular matrix and pro-inflammatory/degradative responses of the tissue. The objective of this study was to determine how magnitude of loading with or without injury and/or pro-inflammatory stimulation affects the metabolic response of a whole-organ rat tail IVD explant model. Methods: Endplate-IVD-endplate whole-organ explants were harvested from the tails of rats. Injured groups were punctured with a 20G needle to the center of the nucleus and stimulated with or without 10ng/mL IL-1[beta]. Explants were cultured in the Flexcell system at various loading magnitudes for 3 days. Media was collected for biomarker analysis and tissue for extracellular matrix composition analysis. Results: Uninjured explants had increased pro-inflammatory, anti-degradative, and degradative biomarker release with the application of load. There was also an increased release of glycosaminoglycan (GAG) to the media and decreased tissue GAG with load. With injury, there was a general decrease in pro-inflammatory and anti-degradative biomarker release and increased GAG released to the media with the application of load. In injured and IL-1[beta] stimulated explants, there was increased pro-inflammatory and anti-degradative biomarker release to the media, decreased degradative activity, and decreased GAG release to the media with the application of load. Discussion: These results suggest that, with uninjured and non-inflamed discs, loading is associated with relevant pro-inflammatory and degradative responses in a magnitude-dependent manner. Additionally, loading may counteract the inflammatory and degradative responses in injured discs associated with pro-inflammatory cytokine stimulation. These differences have clinical importance as they can help in the development of methods to mitigate risk for IVD degeneration. Further study is required to elucidate the mechanisms underlying IVD responses to load and/or injury with or without cytokine stimulation and translate these findings to the clinical setting.
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