Alpha11 beta1 integrin-dependent regulation of periodontal ligament function in the erupting mouse incisor.
The fibroblast integrin alpha11beta1 is a key receptor for fibrillar collagens. To study the potential function of alpha11 in vivo, we generated a null allele of the alpha11 gene. Integrin alpha11(-/-) 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. alpha11beta1-defective embryonic fibroblasts displayed severe defects in vitro, characterized by (i) greatly reduced cell adhesion and spreading on collagen I, (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 alpha11(-/-) cells. We show that alpha11beta1 is the major receptor for collagen I on mouse embryonic fibroblasts and suggest that alpha11beta1 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 alpha11beta1 integrin during tooth eruption.
Popova
Svetlana N
SN
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen, Norway.
Barczyk
Malgorzata
M
Tiger
Carl-Fredrik
CF
Beertsen
Wouter
W
Zigrino
Paola
P
Aszodi
Attila
A
Miosge
Nicolai
N
Forsberg
Erik
E
Gullberg
Donald
D
D000818:Animals; D001755:Blastocyst; D002461:Cell Line, Transformed; D002465:Cell Movement; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006720:Homozygote; D007150:Immunohistochemistry; D007180:Incisor / Q000166:cytology / Q000502:physiology*; D016023:Integrins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D038981:Receptors, Collagen / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014078:Tooth Eruption
D024042:Collagen Type I; D024141:Collagen Type IV; D005353:Fibronectins; D016023:Integrins; D038981:Receptors, Collagen; C467800:integrin alpha11beta1