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Abstract
Low back pain is the most common musculoskeletal problem and the single most common cause of disability, often attributed to degeneration of the intervertebral disc. Lack of effective treatment is directly related to our limited understanding of the pathways responsible for maintaining disc health. While transcriptional analysis has permitted initial insights into the biology of the intervertebral disc, complete proteomic characterization is required. We therefore employed liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) protein/peptide separation and mass spectrometric analyses to characterize the protein content of intervertebral discs from skeletally mature wild-type mice. A total of 1360 proteins were identified and categorized using PANTHER. Identified proteins were primarily intracellular/plasma membrane (35%), organelle (30%), macromolecular complex (10%), extracellular region (9%). Molecular function categorization resulted in three distinct categories: catalytic activity (33%), binding (molecule interactions) (29%), and structural activity (13%). To validate our list, we confirmed the presence of 14 of 20 previously identified IVD-associated markers, including matrix proteins, transcriptional regulators, and secreted proteins. Immunohistochemical analysis confirmed distinct localization patterns of select protein with the intervertebral disc. Characterization of the protein composition of healthy intervertebral disc tissue is an important first step in identifying cellular processes and pathways disrupted during aging or disease progression.
Highlights
Non-specific low back pain has become one of the most common health problems worldwide, with recent reports indicating a lifetime prevalence as high as 84% [1]
Characterization based on protein class was performed, with proteins categorized into 27 classes, with nucleic acid binding (11%) being the most common, followed by cytoskeletal proteins (11%), hydrolases (9%), enzyme modulators (9%) and receptors (7%) (Fig. 1D)
This study provides the first proteome database of intervertebral disc (IVD) tissue from healthy, skeletally mature mice
Summary
Non-specific low back pain has become one of the most common health problems worldwide, with recent reports indicating a lifetime prevalence as high as 84% [1]. According to the most recent Global Burden of Disease study [2] back pain is the single most common cause of disability, with a global prevalence of 23%, causing chronic disability in approximately 12% of the population [1]. While the prevalence of low back pain has increased over the past three decades [3], current treatment options do not adequately provide improved outcomes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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