Transcript levels of major MMPs and ADAMTS-4 in relation to the clinicopathological profile of patients with lumbar disc herniation

Abstract

The involvement of matrix metalloproteinases (MMPs) in both the pathogenesis of intervertebral disc (ID) herniation and the spontaneous regression of herniated ID fragments remains only partially elucidated. The purpose of the present study was to simultaneously examine the transcript levels of a large number of MMPs (-1, -3, -8, -9, -13 and -14) and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs) and to investigate their correlation with the clinicopathologic profile of patients suffering from symptomatic lumbar ID herniation. mRNA expression levels were determined by means of the real-time polymerase chain reaction in 63 herniated and 10 control ID specimens. Our results showed multiple positive correlations among all MMPs and ADAMTS-4 mRNA in herniated samples, indicating their possible synergistic effect in ID herniation. MMP-9 and -13 mRNA levels were significantly elevated in patients with chronic pain, presumably as a consequence of neovascularization and chronic inflammation. Smoking habits were found to have a negative dose-dependent effect on the transcript levels of MMP-3 and MMP-13 and a positive correlation with pain intensity, suggesting an unfavorable role for smoking in the regression process of herniated disc fragments. Our findings provide evidence of the molecular portrait of MMPs and ADAMTS-4 in lumbar ID herniation, as well as of its association with the clinicopathological profile of the patients included in this study, reinforcing the hypothesis of MMPs involvement in the natural history of ID herniation. However, further studies are necessary to elucidate the exact role of MMPs in the resorption process of herniated lumbar discs.

Molecular profile of major growth factors in lumbar intervertebral disc herniation: Correlation with patient clinical and epidemiological characteristics

“…Both TNF-α and IL-1 have been shown to interact with numerous GFs in human degenerated discs and trigger a sequence of macrophage and MMP activation that potentiates the spontaneous resorption of herniated ID fragments (20–22). Multiple positive correlations between numerous MMPs have also been demonstrated in human ID herniation (5). Our findings, therefore, confirm a synergistic activation of GFs in ID herniation as part of a metabolic cascade that ultimately promotes the regression process of herniated discs.…”

“…In addition, a positive correlation has been found between the regression of disc herniation and the remission of symptoms (3,4). Various molecules, such as pro-inflammatory cytokines, growth factors (GFs) and matrix metalloproteinases (MMPs) have been implicated in the mechanisms that regulate ID degradation and herniation, as well as the spontaneous resorption of herniated disc fragments (5). …”

ADAMTS‐4 and ADAMTS‐5 expression in human temporomandibular joint discs with internal derangement, correlates with degeneration

“…The aggregates, with their high negative charge, attract water molecules and endow cartilage with resistibility to compression and deformation. Therefore, aggregate formation is of much significance, as it ensures the retention of aggrecan within the collagen network . Loss of aggrecan is considered to be a critical early event in the destruction of articular disc and cartilage, followed by degradation of collagen fibrils and irreversible mechanical failure of tissue.…”

“…Several studies have been carried out, in joints other than TMJ, and their pivotal roles in disc and articular cartilage diseases, have been pointed out . As far as, TMJ disc is concerned except for one study which demonstrated immunohistochemically an up‐regulation of ADAMTS‐5 (but not ADAMTS‐4) in TMJ discs and another one, which detected aggrenases by Western blot, in synovial fluid from diseased TMJ , literature is lacking.…”

“…ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) are a large family of metalloproteases different from MMPs, which have received increasing attention in recent years . They have been suggested to play a major role in the pathogenesis of intervertebral disc degeneration because they responsible for proteoglycans degradation .…”