Expression of ADAMTS-4 (aggrecanase-1) and possible involvement in regression of lumbar disc herniation.
METHODS
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.


BACKGROUND
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.
Hatano
Eiju
E
Department of Pathology, Kanazawa Medical University, Ishikawa, Japan.
Fujita
Takuya
T
Ueda
Yoshimichi
Y
Okuda
Tetsuhito
T
Katsuda
Shogo
S
Okada
Yasunori
Y
Matsumoto
Tadami
T
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071121:ADAMTS4 Protein; D000328:Adult; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000201:enzymology / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D008159:Lumbar Vertebrae / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011348:Procollagen N-Endopeptidase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012075:Remission, Spontaneous; D014018:Tissue Distribution
D012333:RNA, Messenger; D051722:ADAM Proteins; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human