Expression of hypoxia-inducible factor-1α, vascular endothelial growth factor, and matrix metalloproteinases 1, 3, and 9 in hypertrophied ligamentum flavum.
METHODS
Immunohistological study.


OBJECTIVE
To elucidate the role of matrix metalloproteinases (MMPs), hypoxia-inducible factor-1α (HIF), and vascular endothelial growth factor (VEGF) in the hypertrophied ligamentum flavum (LF) obtained from patients with lumbar spinal stenosis (LSS).


BACKGROUND
The most common spinal disorder in the elderly is LSS, which results in part from LF hypertrophy. Although prior histologic and immunochemical studies have been performed in this area, the pathophysiology of loss of elasticity and hypertrophy is not completely understood.


METHODS
LF samples of 38 patients with LSS were harvested during spinal decompression. Twelve LF samples obtained from patients with disk herniation and no visible degeneration on preoperative magnetic resonance imaging were obtained as controls. Samples were dehydrated and paraffin embedded. For immunohistochemical determination of VEGF, HIF, and MMPs 1, 3, and 9 expression, slices were stained with VEGF, HIF, and MMP antibody dilution. Neovessel density and number of elastic fibers were counted after Masson-Goldner staining. LF hypertrophy and cross-sectional area (CSA) were measured on T1-weighted magnetic resonance imaging.


RESULTS
MMPs 1, 3, 9 and VEGF expression were significantly increased in the hypertrophy group (P<0.05). HIF expression was negative in both groups. Vessel density was increased in the hypertrophy group, although this was not statistically significant. The number of elastic fibres was significantly higher in the control group. In the hypertrophy group, LF thickness was significantly increased, whereas CSA was significantly decreased. There was a statistical correlation between LF thickness, CSA, MMP, and VEGF expression in the hypertrophy group (P<0.05).


CONCLUSIONS
LF hypertrophy is accompanied by increased MMPs 1, 3, 9 and VEGF expression. Neovessel density is increased in hypertrophied LF. HIF is not expressed in hypertrophied LF.
*Department of Orthopedics, University Hospital Goettingen, Goettingen †Department of Orthopedics and Rheumatology, University Hospital Marburg, Marburg ‡Orthomedic Gelenkzentrum Offenbach, Germany §Department of Neurosurgery, University Hospital Marburg, Marburg.
Stefan
S
Lakemeier
Markus D
MD
Schofer
Lisa
L
Foltz
Raphael
R
Schmid
Turgay
T
Efe
Jochen
J
Rohlfs
Susanne
S
Fuchs-Winkelmann
Bilal F
BF
El-Zayat
Jürgen R J
JR
Paletta
Christian
C
Foelsch
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D006801:Humans; D006984:Hypertrophy / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007405:Intervertebral Disc Displacement; D017843:Ligamentum Flavum / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology*; D008159:Lumbar Vertebrae / Q000201:enzymology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D011859:Radiography; D013130:Spinal Stenosis / Q000201:enzymology / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D055815:Young Adult
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1