Laminin alpha2 is essential for odontoblast differentiation regulating dentin sialoprotein expression.
Laminin alpha2 is subunit of laminin-2 (alpha2beta1gamma1), which is a major component of the muscle basement membrane. Although the laminin alpha2 chain is expressed in the early stage of dental mesenchyme development and localized in the tooth germ basement membrane, its expression pattern in the late stage of tooth germ development and molecular roles are not clearly understood. We analyzed the role of laminin alpha2 in tooth development by using targeted mice with a disrupted lama2 gene. Laminin alpha2 is expressed in dental mesenchymal cells, especially in odontoblasts and during the maturation stage of ameloblasts, but not in the pre-secretory or secretory stages of ameloblasts. Lama2 mutant mice have thin dentin and a widely opened dentinal tube, as compared with wild-type and heterozygote mice, which is similar to the phenotype of dentinogenesis imperfecta. During dentin formation, the expression of dentin sialoprotein, a marker of odontoblast differentiation, was found to be decreased in odontoblasts from mutant mice. Furthermore, in primary cultures of dental mesenchymal cells, dentin matrix protein, and dentin sialophosphoprotein, mRNA expression was increased in laminin-2 coated dishes but not in those coated with other matrices, fibronectin, or type I collagen. Our results suggest that laminin alpha2 is essential for odontoblast differentiation and regulates the expression of dentin matrix proteins.
Yuasa
Kenji
K
Division of Pediatric Dentistry, Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
Fukumoto
Satoshi
S
Kamasaki
Yoko
Y
Yamada
Aya
A
Fukumoto
Emiko
E
Kanaoka
Kazuhiro
K
Saito
Kan
K
Harada
Hidemitsu
H
Arikawa-Hirasawa
Eri
E
Miyagoe-Suzuki
Yuko
Y
Takeda
Shinichi
S
Okamoto
Kuniaki
K
Kato
Yuzo
Y
Fujiwara
Taku
T
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003743:Dental Enamel / Q000378:metabolism; D003804:Dentin / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005353:Fibronectins / Q000378:metabolism; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D009154:Mutation; D009804:Odontoblasts / Q000166:cytology* / Q000378:metabolism; D053495:Osteopontin; D010641:Phenotype; D010750:Phosphoproteins; D011485:Protein Binding; D011498:Protein Precursors; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000096:biosynthesis*; D014070:Tooth / Q000196:embryology / Q000648:ultrastructure; D000099311:Dentin Sialophosphoprotein
D003094:Collagen; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D053495:Osteopontin; D010750:Phosphoproteins; D011498:Protein Precursors; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C506896:Spp1 protein, mouse; C102645:laminin alpha 2