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 t...

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Bibliographic Details
Published in:The Journal of biological chemistry 2017-05, Vol.292 (19), p.7745-7760
Main Authors: Sens, Carla, Huck, Katrin, Pettera, Stefan, Uebel, Stephan, Wabnitz, Guido, Moser, Markus, Nakchbandi, Inaam A.
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Animals, Newborn
Cell Adhesion
Cell Biology
Cell Differentiation
differentiation
DNA, Complementary - metabolism
Enzyme-Linked Immunosorbent Assay
Extracellular Matrix - metabolism
fibronectin
Fibronectins - metabolism
Green Fluorescent Proteins - metabolism
Humans
integrin
Integrin alpha4beta1 - metabolism
Integrin alphaVbeta3 - metabolism
Mice
Oligopeptides - metabolism
osteoblast
Osteoblasts - cytology
Osteoblasts - metabolism
Osteogenesis
Protein Binding
Protein Domains
Protein Isoforms
RNA, Small Interfering - metabolism
Signal Transduction
signaling
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Summary: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 vivo findings 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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M116.739987