Influence of collagen-based integrin α 1 and α 2 mediated signaling on human mesenchymal stem cell osteogenesis in three dimensional contexts

• Published in: Journal of biomedical materials research. Part A Vol. 106; no. 10; pp. 2594 - 2604
• Main Authors: Becerra-Bayona, Silvia M, Guiza-Arguello, Viviana R, Russell, Brooke, Höök, Magnus, Hahn, Mariah S
• Format: Journal Article
• Language: English
• Published: United States 01.10.2018
• Subjects: Biomarkers - metabolism; Collagen - metabolism; Humans; Hydrogels - pharmacology; Integrin alpha1 - metabolism; Integrin alpha2 - metabolism; MAP Kinase Signaling System - drug effects; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Osteogenesis - drug effects; Osteopontin - metabolism; Polyethylene Glycols - pharmacology; Protein Subunits - metabolism; Signal Transduction; Sp7 Transcription Factor - metabolism; Tensile Strength; collagen-mimetic proteins; integrin α2; integrin α1; osteogenesis; human mesenchymal stem cells
• ISSN: 1549-3296; 1552-4965
• DOI: 10.1002/jbm.a.36451

Collagen I interactions with integrins α and α are known to support human mesenchymal stem cell (hMSC) osteogenesis. Nonetheless, elucidating the relative impact of specific integrin interactions has proven challenging, in part due to the complexity of native collagen. In the present work, we employed two collagen-mimetic proteins-Scl2-2 and Scl2-3- to compare the osteogenic effects of integrin α versus α signaling. Scl2-2 and Scl2-3 were both derived from Scl2-1, a triple helical protein lacking known cell adhesion, cytokine binding, and matrix metalloproteinase sites. However, Scl2-2 and Scl2-3 were each engineered to display distinct collagen-based cell adhesion motifs: GFPGER (binding integrins α and α ) or GFPGEN (binding only integrin α ), respectively. hMSCs were cultured within poly(ethylene glycol) (PEG) hydrogels containing either Scl2-2 or Scl2-3 for 2 weeks. PEG-Scl2-2 gels were associated with increased hMSC osterix expression, osteopontin production, and calcium deposition relative to PEG-Scl2-3 gels. These data indicate that integrin α signaling may have an increased osteogenic effect relative to integrin α . Since p38 is activated by integrin α but not by integrin α , hMSCs were further cultured in PEG-Scl2-2 hydrogels in the presence of a p38 inhibitor. Results suggest that p38 activity may play a key role in collagen-supported hMSC osteogenesis. This knowledge can be used toward the rational design of scaffolds which intrinsically promote hMSC osteogenesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2594-2604, 2018.