α11β1 integrin-dependent regulation of periodontal ligament function in the erupting mouse incisor

The fibroblast integrin alpha 11 beta 1 is a key receptor for fibrillar collagens. To study the potential function of alpha 11. in vivo, we generated a null allele of the alpha 11 gene. Integrin alpha 1(-/-) mice are viable and fertile but display dwarfism with increased mortality, most probably due to severely defective incisors. Mutant incisors are characterized by disorganized periodontal ligaments, whereas molar ligaments appear normal. The primary defect in the incisor ligament leads to halted tooth eruption. alpha 11 beta 1-defective embryonic fibroblasts displayed severe defects in vitro, characterized by (i) greatly reduced cell adhesion and spreading on collagen 1, (ii) reduced ability to retract collagen lattices, and (iii) reduced cell proliferation. Analysis of matrix metalloproteinase in vitro and in vivo revealed disturbed MMP13 and MMP14 synthesis in alpha 11(-/-) cells. We show that alpha 11 beta 1 is the major receptor for collagen I on mouse embryonic fibroblasts and suggest that alpha 11 beta 1 integrin is specifically required on periodontal ligament fibroblasts for cell migration and collagen reorganization to help generate the forces needed for axial tooth movement. Our data show a unique role for alpha 11 beta 1 integrin during tooth eruption.