Expression of ADAMTS-4 (aggrecanase-1) and Possible Involvement in Regression of Lumbar Disc Herniation

Study design Examination of ADAMTS-4 expression, and cellular lineages, distribution, and numbers of ADAMTS-4 (aggrecanase-1) expressing cells in herniated lumbar intervertebral discs. Objective To determine the expression of ADAMTS-4, a metalloproteinase capable of digesting aggrecan, and its role in herniated lumbar intervertebral disc degradation. Summary of background data Matrix metalloproteinases degrade extracellular matrix of herniated discs, but the mechanism of aggrecan degradation, the major component of intervertebral discs, is poorly understood. Methods Surgically resected herniated lumbar intervertebral discs from 22 patients were subclassified into protrusion, subligamentous extrusion, transligamentous extrusion, and sequestration types. Reverse transcriptase polymerase chain reaction, Western blot, and immunohistochemistry were used to evaluate ADAMTS-4 messenger ribonucleic acid and protein expression. Results Expression of ADAMTS-4 messenger ribonucleic acid and protein was shown in the samples of herniated lumbar intervertebral discs. Immunohistochemical staining showed that ADAMTS-4 was mainly localized in CD68-positive mononuclear cells in granulation and adjacent disc tissues. ADAMTS-4 positive cell counts were significantly higher in transligamentous extrusion and sequestration than protrusion and subligamentous extrusion types. Alcian blue staining showed a decrease of proteoglycan in transligamentous extrusion and sequestration cases. Conclusions Macrophages infiltrating granulation and adjacent disc tissues express ADAMTS-4, suggesting its involvement in herniated disc regression.