The expression of metalloproteinases in the lumbar disc correlates strongly with Pfirrmann MRI grades in lumbar spinal fusion patients

Abstract

Introduction: Increased catabolism of the extracellular matrix is observed under degenerative disc disease (DDD). The cleavage of extracellular matrix proteins in the nucleus pulposus (NP) by either matrix metalloproteinases (MMPs) or a disintegrin and metalloproteinases with thrombospondin motifs (ADAMTSs) is believed to be involved in the degeneration, but the mechanisms are not known. Research question: Here, we examine the correlation between expression of several MMPs and ADAMTSs subtypes in lumbar discs from 34 patients with low back pain (LBP) undergoing 1-2 level lumbar fusion surgery (L4/L5 and/or L5/S1) for DDD with or without spondylolisthesis. Materials and Methods: The mRNA levels of MMPs (subtypes 1, 2, 3, 10, and 13) and ADAMTSs (subtypes 1, 4, and 5) were analyzed using quantitative real-time polymerase chain reaction (RT-qPCR) and correlated to the Pfirrmann magnetic resonance imaging classification system (grade I-V) of lumbar DDD. Results: We find a highly significant positive correlation between Pfirrmann grades and the gene expression of MMP1 (r=0.67, p=0.0001), MMP3 (r=0.61, p=0.0002), MMP10 (r=0.6701, p=0.0001), MMP13 (r=0.48, p=0.004), ADAMTS1 (r=0.67, p=0.0001), and ADAMTS5 (r=0.53, p=0.0017). The similar regulation of these transcript suggests their involvement in disc degeneration. Interestingly, a post hoc analysis (uncorrected p-values) also demonstrated a positive correlation between expression of TNF-α, IL-6 and both ADAMTSs/MMPs and the Pfirrmann grades. Discussion and Conclusion: These findings show that disc degradation in DDD is strongly associated with the expression of some metalloproteinases.

Keywords

• ADAMTS
• Disc Degeneration
• MMP
• mRNA
• Real-time PCR