Hypertrophy of the lumbar ligamentum flavum is associated with inflammation-related TGF-β expression.
BACKGROUND
Despite the significance of hypertrophy of the ligamentum flavum (HLF) in the disease progress of neurogenic claudication, the cellular mechanisms underlying the gradual fibrotic thickening of the ligamentum flavum remain poorly understood. The aim of our study was to get insight into the contribution of inflammatory mechanisms to the development of hypertrophy.


METHODS
Specimens of hypertrophied ligamenta flava were obtained at surgery from 20 patients with acquired lumbar osteoligamentous spinal canal stenosis from the central part of the ligament. Paraffin sections were stained with hematoxylin and eosin and Elastica van Gieson to evaluate extracellular matrix architecture, and immunohistochemistry was performed to characterize the inflammatory reaction and the sources of transforming growth factor beta (TGF-β) expression. Sections of normal ligamenta flava obtained from corresponding anatomical sites and stained in parallel served as a control.


RESULTS
HLF was characterized by a considerable distortion of the elastic matrix and fibrotic transformation by extracellular collagen deposition. All specimens showed highly inflammatory cellular infiltrates confined to regions exhibiting marked degeneration of the elastic matrix composed mainly of macrophages, scattered T lymphocytes, and neovascularization, thus representing a chronic inflammation. Surprisingly, macrophages as well as vascular endothelial cells but not fibroblasts showed a strong expression of TGF-β, a strong inducer of extracellular collagen deposition.


CONCLUSIONS
Macrophages were identified as a major cellular source of TGF-β in advanced HLF and may perpetuate further hypertrophy. This finding suggests that modulating the immune response locally or systemically could prove to be effective for impeding the disease progress.
Löhr
Mario
M
Department of General Neurosurgery, University Hospital of Cologne, Kerpener Strasse 62, 50924 Cologne, Germany. loehr.m@nch.uni-wuerzburg.de
Hampl
Jürgen Anton
JA
Lee
Jin Yul
JY
Ernestus
Ralf-Ingo
RI
Deckert
Martina
M
Stenzel
Werner
W
D000368:Aged; D000369:Aged, 80 and over; D003094:Collagen / Q000378:metabolism; D005110:Extracellular Space / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D006984:Hypertrophy; D018836:Inflammation Mediators / Q000378:metabolism*; D017843:Ligamentum Flavum / Q000378:metabolism* / Q000473:pathology*; D008159:Lumbar Vertebrae / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013130:Spinal Stenosis / Q000378:metabolism* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D018836:Inflammation Mediators; D016212:Transforming Growth Factor beta; D003094:Collagen