title: A role for decorin in the structural organization of periodontal ligament.
abstract: Decorin is a small leucine-rich proteoglycan that interacts with several matrix molecules, including various types of collagen and growth factors, and suppresses the growth of neoplastic cells by an epidermal growth factor (EGF) receptor-mediated pathway. Decorin is abundantly expressed in the periodontal connective tissues during development and tissue maintenance. In periodontal disease, which is one of the most common diseases in the human kind, the level of decorin is decreased in the periodontal connective tissue. Abnormal expression of decorin may also associate with certain inherited disorders that involve increased susceptibility to severe periodontal disease in the early childhood. Therefore, we investigated the periodontal tissues of mice with targeted disruption of the decorin gene. Gross and microscopic analyses showed that decorin-deficient mice appeared to have normal tooth development and eruption, and there were no signs of periodontal disease. However, electron microscopic analysis revealed abnormal morphology and organization of the collagen fibrils in the periodontal ligament. The number of periodontal ligament fibroblasts in the decorin-deficient mice was also increased about two-fold as compared with the wild-type mice. In cell culture, ectopic overexpression of decorin in NIH 3T3 fibroblasts or decorin added exogenously to periodontal fibroblasts suppressed cell growth. However, blocking the EGF receptor tyrosine kinase activity did not prevent the decorin-elicited growth suppression in periodontal fibroblasts. Additionally, decorin did not induce a marked increase in the relative expression of p21 mRNA in periodontal fibroblasts. Therefore, decorin appeared to regulate growth of normal periodontal fibroblasts by a mechanism distinct from that reported for neoplastic cells. The findings demonstrate that decorin plays a role in the organization of collagen fibrils and regulates cell proliferation in the periodontal ligament.
authors.affiliation: Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, Canada. lhakkine@interchange.ubc.ca
authors.forename: L
authors.initials: L
authors.lastname: Häkkinen
authors.forename: S
authors.initials: S
authors.lastname: Strassburger
authors.forename: V M
authors.initials: VM
authors.lastname: Kähäri
authors.forename: P G
authors.initials: PG
authors.lastname: Scott
authors.forename: I
authors.initials: I
authors.lastname: Eichstetter
authors.forename: R V
authors.initials: RV
authors.lastname: Lozzo
authors.forename: H
authors.initials: H
authors.lastname: Larjava
mesh_terms: D016475:3T3 Cells; D000375:Aging / Q000502:physiology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D058575:Decorin; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D010513:Periodontal Ligament / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011799:Quinazolines; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D011799:Quinazolines; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D020032:Tyrphostins; C101044:RTKI cpd