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.
Eur Spine J. 2011 May;20(5):781-90. doi: 10.1007/s00586-010-1573-9. Epub 2010 Sep 22.
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.
基质金属蛋白酶(MMPs)在椎间盘(ID)突出症的发病机制和突出 ID 片段的自发消退中都有参与,但目前仍不完全清楚。本研究的目的是同时检测大量 MMPs(-1、-3、-8、-9、-13 和-14)和 ADAMTS-4(具有血小板反应蛋白基序的解整合素和金属蛋白酶)的转录水平,并研究它们与患有症状性腰椎 ID 突出症的患者的临床病理特征之间的相关性。通过实时聚合酶链反应,在 63 个突出和 10 个对照 ID 标本中测定了 mRNA 表达水平。我们的结果表明,在突出的样本中,所有 MMPs 和 ADAMTS-4 mRNA 之间存在多种正相关,表明它们在 ID 突出中可能具有协同作用。MMP-9 和 -13 mRNA 水平在慢性疼痛患者中显著升高,可能是新生血管形成和慢性炎症的结果。吸烟习惯被发现对 MMP-3 和 MMP-13 的转录水平有负剂量依赖性的影响,并与疼痛强度呈正相关,这表明吸烟在椎间盘突出物的消退过程中起不利作用。我们的研究结果为 MMPs 和 ADAMTS-4 在腰椎 ID 突出中的分子特征提供了证据,以及其与纳入本研究患者的临床病理特征的相关性,这进一步证实了 MMPs 参与 ID 突出的自然史的假说。然而,需要进一步的研究来阐明 MMPs 在椎间盘突出的吸收过程中的确切作用。