The increased expression of matrix metalloproteinases associated with elastin degradation and fibrosis of the ligamentum flavum in patients with lumbar spinal stenosis.
BACKGROUND
One of the characteristics of spinal stenosis is elastin degradation and fibrosis of the extracellular matrix of the ligamentum flavum. However, there have been no investigations to determine which biochemical factors cause these histologic changes. So we performed the current study to investigate the hypothesis that matrix metalloproteinases (MMPs), which possess the ability to cause extracellular matrix remodeling, may play a role as a mediator for this malady in the ligamentum flavum.


METHODS
The ligamentum flavum specimens were surgically obtained from thirty patients with spinal stenosis, as well as from 30 control patients with a disc herniation. The extents of ligamentum flavum elastin degradation and fibrosis were graded (grade 0-4) with performing hematoxylin-eosin staining and Masson's trichrome staining, respectively. The localization of MMP-2 (gelatinase), MMP-3 (stromelysin) and MMP-13 (collagenase) within the ligamentum flavum tissue was determined by immunohistochemistry. The expressions of the active forms of MMP-2, MMP-3 and MMP-13 were determined by western blot analysis, and the blots were quantified using an imaging densitometer. The histologic and biochemical results were compared between the two conditions.


RESULTS
Elastin degradation and fibrosis of the ligamentum flavum were significantly more severe in the spinal stenosis samples than that in the disc herniation samples (3.14 +/- 0.50 vs. 0.55 +/- 0.60, p < 0.001; 3.10 +/- 0.57 vs. 0.76 +/- 0.52, p < 0.001, respectively). The expressions of the active form of MMPs were identified in all the ligamentum flavums of the spinal stenosis and disc herniation patients. The expressions of active MMP-2 and MMP-13 were significantly higher in the spinal stenosis samples than that in the disc herniation samples (both p < 0.05). The expression of active MMP-3 was slightly higher in the spinal stenosis samples than that in the disc herniation samples, but the difference was not statistically significant (p = 0.131). MMP-2, -3, and -13 were positively stained on the ligamentum flavum fibroblasts.


CONCLUSIONS
The current results suggest that the increased expression of active MMPs by the ligamentum flavum fibroblasts might be related to the elastin degradation and fibrosis of the ligamentum flavum in the patients who suffer with lumbar spinal stenosis.
Park
Jong-Beom
JB
Department of Orthopaedic Surgery, The Catholic University of Korea School of Medicine, Uijeongbu, Korea. spinepjb@catholic.ac.kr
Kong
Chae-Gwan
CG
Suhl
Kyung-Hwan
KH
Chang
Eun-Deok
ED
Riew
K Daniel
KD
D000368:Aged; D015153:Blotting, Western; D004549:Elastin / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D017843:Ligamentum Flavum / Q000378:metabolism* / Q000473:pathology; D008159:Lumbar Vertebrae; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D013130:Spinal Stenosis / Q000378:metabolism* / Q000473:pathology
D004549:Elastin; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2