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Integrin α4 mediates ATDC5 cell adhesion to negatively charged synthetic polymer hydrogel leading to chondrogenic differentiation.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Jul 12; Vol. 528 (1), pp. 120-126. Date of Electronic Publication: 2020 May 23. - Publication Year :
- 2020
-
Abstract
- Negatively charged synthetic hydrogels have been known to facilitate various cellular responses including cell adhesion, proliferation, and differentiation; however, the molecular mechanism of hydrogel-dependent control of cell behavior remains unclear. Recently, we reported that negatively charged poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) gel induces chondrogenic differentiation of ATDC5 cells via novel protein reservoir function. In this study, we identified the cell adhesion molecules binding to PAMPS gels that act as mechanoreceptors. First, we performed a pull-down assay by particle gels using cell membrane proteins of ATDC5, and found that multiple membrane proteins bound to the PAMPS gel, whereas the uncharged poly(N,N'-dimethylacrylamide) gel as control did not bind to any membrane proteins. Western blot analysis indicated differential binding of integrin (ITG) isoforms to the PAMPS gel, in which the α4 isoform, but not α5 and αv, efficiently bound to the PAMPS gel. ITG α4 knockdown decreased cell spreading of ATDC5 on PAMPS gels, whereas the enhanced expression increased the behavior. Furthermore, ITG α4 depletion suppressed PAMPS gel-induced expression of bone morphogenic protein (BMP) 4 contributing to chondrogenic differentiation, in concordance with the reduction of ERK activation. These results demonstrated that membrane protein binding to PAMPS gels occurred in a charge-dependent manner, and that ITG α4 plays a crucial role in cell spreading on PAMPS gels and acts as a mechanoreceptor triggering cellular signaling leads to chondrogenic differentiation.<br />Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Bone Morphogenetic Protein 4 pharmacology
Cell Adhesion drug effects
Cell Line
Cell Movement drug effects
Extracellular Signal-Regulated MAP Kinases metabolism
Gene Knockdown Techniques
Humans
Membrane Proteins metabolism
Mice
Phosphorylation drug effects
Protein Binding drug effects
Sulfonic Acids chemistry
Cell Differentiation drug effects
Chondrogenesis drug effects
Hydrogels chemistry
Integrin alpha4 metabolism
Polymers chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 528
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 32456794
- Full Text :
- https://doi.org/10.1016/j.bbrc.2020.05.071