Fibronectins containing extradomain A or B enhance osteoblast differentiation via distinct integrins.
Fibronectin is a multidomain protein secreted by various cell types. It forms a network of fibers within the extracellular matrix and impacts intracellular processes by binding to various molecules, primarily integrin receptors on the cells. Both the presence of several isoforms and the ability of the various domains and isoforms to bind to a variety of integrins result in a wide range of effects.In vivofindings suggest that fibronectin isoforms produced by the osteoblasts enhance their differentiation. Here we report that the isoform characterized by the presence of extradomain A activates α4β1 integrin and augments osteoblast differentiation. In addition, the isoform containing extradomain B enhances the binding of fibronectin through the RGD sequence to β3-containing integrin, resulting in increased mineralization by and differentiation of osteoblasts. Our study thus reveals novel functions for two fibronectin isoforms and the mediating receptors in osteoblast differentiation.
From the Max-Planck Institute of Biochemistry, 82152 Martinsried and.|the Institute of Immunology, University of Heidelberg, 69120 Heidelberg, Germany.
Carla
C
Sens
From the Max-Planck Institute of Biochemistry, 82152 Martinsried and.|the Institute of Immunology, University of Heidelberg, 69120 Heidelberg, Germany.
Katrin
K
Huck
From the Max-Planck Institute of Biochemistry, 82152 Martinsried and.
Stefan
S
Pettera
From the Max-Planck Institute of Biochemistry, 82152 Martinsried and.
Stephan
S
Uebel
the Institute of Immunology, University of Heidelberg, 69120 Heidelberg, Germany.
Guido
G
Wabnitz
From the Max-Planck Institute of Biochemistry, 82152 Martinsried and.
Markus
M
Moser
From the Max-Planck Institute of Biochemistry, 82152 Martinsried and inaam.nakchbandi@immu.uni-heidelberg.de.|the Institute of Immunology, University of Heidelberg, 69120 Heidelberg, Germany.
Inaam A
IA
Nakchbandi
D016475:3T3 Cells; D000818:Animals; D000831:Animals, Newborn; D002448:Cell Adhesion; D002454:Cell Differentiation; D018076:DNA, Complementary / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D011485:Protein Binding; D000072417:Protein Domains; D020033:Protein Isoforms; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction
D018076:DNA, Complementary; C067625:FN1 protein, human; D005353:Fibronectins; D039041:Integrin alpha4beta1; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; C047981:arginyl-glycyl-aspartic acid
differentiation; fibronectin; integrin; osteoblast; signaling