Laminin α2 Is Essential for Odontoblast Differentiation Regulating Dentin Sialoprotein Expression

TLDR

Laminin‑α2, a subunit of laminin‑2, is a major basement‑membrane component expressed early in dental mesenchyme but its late‑stage expression and molecular roles remain unclear. The authors examined laminin‑α2 function by generating lama2‑knockout mice and studying tooth development. Laminin‑α2 is expressed in odontoblasts and during ameloblast maturation, and lama2‑knockout mice display thin dentin with open dentinal tubes, reduced dentin sialoprotein expression, and impaired odontoblast differentiation, indicating that laminin‑α2 is essential for odontoblast differentiation and regulation of dentin matrix protein expression.

Abstract

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.