Distinctive localization and function for lumican, fibromodulin and decorin to regulate collagen fibril organization in periodontal tissues.
BACKGROUND
Small leucine-rich proteoglycans (SLRPs) decorin, biglycan, fibromodulin and lumican are secreted extracellular matrix molecules that associate with fibrillar collagens and regulate collagen fibrillogenesis. Collagens are the major extracellular matrix components of periodontal connective tissues where they provide mechanical attachment of the tooth to the bone and gingiva and mediate signals that regulate cell functions, including remodeling of the periodontal ligament and bone. Structural organization of collagen may also be important for the defense against periodontal disease, because in certain conditions abnormal collagen fibrils associate with increased susceptibility to periodontal disease.


OBJECTIVE
The purpose of this study was to find out the role of SLRPs to regulate collagen fibril and fibril bundle formation in periodontal tissues.


METHODS
The localization of SLRPs in human and mouse periodontal tissues was studied using immunohistochemical methods. To assess the function of SLRPs we studied periodontal tissues of mice harboring targeted deletions of decorin, fibromodulin or lumican genes and lumican and fibromodulin double knockout mice using histological and electronmicroscopical methods.


RESULTS
The SLRPs were coexpressed in human and mouse gingival and periodontal ligament connective tissues where they colocalized with collagen fibril bundles. Teeth in the knockout animals were fully erupted and showed normal gross morphology. Targeted deletion of decorin, fibromodulin, lumican or both lumican and fibromodulin resulted in abnormal collagen fibril and fibril bundle morphology that was most evident in the periodontal ligament. Each of the gene deletions resulted in a unique fibril and fibril bundle phenotype.


CONCLUSIONS
These findings indicate that decorin, fibromodulin and lumican coordinately regulate the fibrillar and suprafibrillar organization of collagen in the periodontal ligament.
Matheson
S
S
Department of Oral Biological and Medical Sciences, Laboratory of Periodontal Biology, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.
Larjava
H
H
Häkkinen
L
L
D000293:Adolescent; D000328:Adult; D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000032:analysis / Q000235:genetics / Q000502:physiology; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D005260:Female; D024022:Fibrillar Collagens / Q000737:chemistry* / Q000235:genetics*; D000071235:Fibromodulin; D017353:Gene Deletion; D006801:Humans; D007124:Immunoenzyme Techniques; D007632:Keratan Sulfate / Q000032:analysis / Q000235:genetics / Q000502:physiology; D007930:Leucine; D000071234:Lumican; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010513:Periodontal Ligament / Q000737:chemistry* / Q000502:physiology; D011509:Proteoglycans / Q000032:analysis / Q000235:genetics* / Q000502:physiology*
D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D024022:Fibrillar Collagens; C000604332:Fmod protein, mouse; C000604306:LUM protein, human; C000604307:Lum protein, mouse; D000071234:Lumican; D011509:Proteoglycans; D000071235:Fibromodulin; D007632:Keratan Sulfate; D007930:Leucine