Basement membrane-type heparan sulfate proteoglycan (perlecan) and low-density lipoprotein (LDL) are co-localized in granulation tissues: a possible pathogenesis of cholesterol granulomas in jaw cysts.
BACKGROUND
As perlecan contains a low-density lipoprotein (LDL) receptor-like repeats in the second domain of its core protein, LDL may be bound to perlecan, which is rich in granulation tissues. We wanted to study if this is the case in the cyst wall of radicular cysts, which are often associated with cholesterol granuloma.


METHODS
Thirty-three specimens of radicular cyst with cholesterol granulomas were immunohistochemically examined for comparative localizations of perlecan, apoprotein B (apo B), and oxidized LDL (Ox-LDL), and for mRNA expression levels for perlecan.


RESULTS
Myxoid or edematous stroma of immature granulation tissues was strongly positive for perlecan and simultaneously for apo B and Ox-LDL. Macrophages including foamy cells scattered in the granulation tissues were also immunopositive for Ox-LDL and occasionally for apo B. In situ hybridization showed that fibroblasts, endothelial cells, and pericytes had strong signals for perlecan, which was also confirmed by RT-PCR.


CONCLUSIONS
These results suggest that perlecan, which is abundantly produced and accumulated in the cyst wall of immature granulation tissue, traps Ox-LDL locally, and that Ox-LDL is phagocytosed by macrophages. Thus, LDL-laden foamy macrophages are aggregated in the granulation tissue, and free cholesterol from ruptured macrophages may be concentrated locally to be crystallized, which may induce foreign body granulomas in the cyst wall.
Yamazaki
Manabu
M
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Niigata 951-8514, Japan.
Cheng
Jun
J
Hao
Natsuko
N
Takagi
Ritsuo
R
Jimi
Shiro
S
Itabe
Hiroyuki
H
Saku
Takashi
T
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D001485:Basement Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D006097:Granulation Tissue / Q000378:metabolism; D015745:Granuloma, Foreign-Body / Q000209:etiology*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D011842:Radicular Cyst / Q000150:complications* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001055:Apolipoproteins B; D019812:Heparan Sulfate Proteoglycans; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; C071927:perlecan; D002784:Cholesterol