Focal adhesion signaling affects regeneration by human nucleus pulposus cells in collagen- but not carbohydrate-based hydrogels

Autor: Krouwels, Anita, Melchels, Ferry P W, van Rijen, Mattie H P, Ten Brink, Corlinda B M, Dhert, Wouter J A, Cumhur Öner, F, Tryfonidou, Marianna A, Creemers, Laura B, Faculteit Diergeneeskunde, Orthopedie en neurochirurgie, dCSCA RMSC-1, Sub General Pharmaceutics
Přispěvatelé: Faculteit Diergeneeskunde, Orthopedie en neurochirurgie, dCSCA RMSC-1, Sub General Pharmaceutics
Rok vydání: 2018
Předmět:
0301 basic medicine
Compressive Strength
Nucleus pulposus
Intervertebral Disc Degeneration
02 engineering and technology
Matrix (biology)
Biochemistry
Stiffness
Extracellular matrix
chemistry.chemical_compound
Hyaluronic acid
Glycosaminoglycans
Focal adhesion kinase
Hydrogels
General Medicine
Middle Aged
021001 nanoscience & nanotechnology
Cell biology
Self-healing hydrogels
Collagen
0210 nano-technology
Signal Transduction
Biotechnology
Adult
Nucleus Pulposus
Materials science
Carbohydrates
Biomedical Engineering
Biomaterials
Focal adhesion
03 medical and health sciences
Humans
Regeneration
Protein Kinase Inhibitors
Molecular Biology
Aged
Integrin binding
Focal Adhesions
Staining and Labeling
Regeneration (biology)
DNA
Chondrogenesis
Actins
Vinculin
Hydrogel
030104 developmental biology
Gene Expression Regulation
chemistry
Focal Adhesion Protein-Tyrosine Kinases
Zdroj: Acta Biomaterialia, 66, 238. Elsevier BV
ISSN: 1742-7061
DOI: 10.1016/j.actbio.2017.11.029
Popis: Hydrogel-based 3D cell cultures are an emerging strategy for the regeneration of cartilage. In an attempt to regenerate dysfunctional intervertebral discs, nucleus pulposus (NP) cells can be cultured in hydrogels of various kinds and physical properties. Stiffness sensing through focal adhesions is believed to direct chondrogenesis, but the mechanisms by which this works are largely unknown. In this study we compared focal adhesion formation and glycosaminoglycan (GAG) deposition by NP cells in a range of hydrogels. Using a focal adhesion kinase (FAK) inhibitor, we demonstrated that focal adhesion signaling is involved in the response of NP cells in hydrogels that contain integrin binding sites (i.e. methacrylated gelatin (gelMA) and type II collagen), but not in hydrogels deplete from integrin binding sites such as alginate and agarose, or CD44-binding hydrogels based on hyaluronic acid. As a result of FAK inhibition we observed enhanced proteoglycan production in gelMA, but decreased production in type II collagen hydrogels, which could be explained by alteration in cell fate as supported by the increase in the adipogenic marker peroxisome proliferator-activated receptor gamma (PPARy). Furthermore, GAG deposition was inversely proportional to polymer concentration in integrin-binding gelMA, while no direct relationship was found for the non-integrin binding gels alginate and agarose. This corroborates our finding that focal adhesion formation plays an important role in NP cell response to its surrounding matrix. Statement of Significance Biomaterials are increasingly being investigated for regenerative medicine applications, including regeneration of the nucleus pulposus. Cells interact with their environment and are influenced by extracellular matrix or polymer properties. Insight in these interactions can improve regeneration and helps to understand degeneration processes. The role of focal adhesion formation in the regenerative response of nucleus pulposus cells is largely unknown. Therefore, the relation between materials, stiffness and focal adhesion formation is studied here.
Databáze: OpenAIRE
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