title: 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.
authors.affiliation: Laboratory of Virology, Medical School, University of Crete, and Department of Orthopedics and Traumatology, University Hospital of Heraklion, P.O. Box 1527, 710 03, Crete, Heraklion, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Tsarouhas
authors.forename: Giannoula
authors.initials: G
authors.lastname: Soufla
authors.forename: Pavlos
authors.initials: P
authors.lastname: Katonis
authors.forename: Dritan
authors.initials: D
authors.lastname: Pasku
authors.forename: Antonis
authors.initials: A
authors.lastname: Vakis
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000502:physiology; D000071121:ADAMTS4 Protein; D000328:Adult; D000368:Aged; D015897:Comorbidity / Q000639:trends; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007403:Intervertebral Disc / Q000201:enzymology* / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D011348:Procollagen N-Endopeptidase / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D012333:RNA, Messenger; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human