The effect of collagen I mimetic peptides on mesenchymal stem cell adhesion and differentiation, and on bone formation at hydroxyapatite surfaces

Abstract

Integrin-binding peptides increase cell adhesion to naive hydroxyapatite (HA), however, in the body, HA becomes rapidly modified by protein adsorption. Previously we reported that, when combined with an adsorbed protein layer, RGD peptides interfered with cell adhesion to HA. In the current study we evaluated mesenchymal stem cell (MSC) interactions with HA disks coated with the collagen-mimetic peptides, DGEA, P15 and GFOGER. MSCs adhered equally well to disks coated with DGEA, P15, or collagen I, and all three substrates, but not GFOGER, supported greater cell adhesion than uncoated HA. When peptide-coated disks were overcoated with proteins from serum or the tibial microenvironment, collagen mimetics did not inhibit MSC adhesion, as was observed with RGD, however neither did they enhance adhesion. Given that activation of collagen-selective integrins stimulates osteoblastic differentiation, we monitored osteocalcin secretion and alkaline phosphatase activity from MSCs adherent to DGEA or P15-coated disks. Both of these osteoblastic markers were upregulated by DGEA and P15, in the presence and absence of differentiation-inducing media. Finally, bone formation on HA tibial implants was increased by the collagen-mimetics. Collectively these results suggest that collagen-mimetic peptides improve osseointegration of HA, most probably by stimulating osteoblastic differentiation, rather than adhesion, of MSCs.

Osteoinduction by Ca-P biomaterials implanted into the muscles of mice

“…Fellah et al (2007; recently reported that the inflammatory cytokines, e.g., IL-6 and TNF-α, released by macrophages stimulated by BCP microparticles, may have both positive and negative effects on new bone formation. However, the very little related research that labelled the marker molecules expressed by the osteocytes or osteoblasts has been performed and was most likely due to the limitation of animal models to some extent (Hennessy et al, 2009). In this study, we observed bone formation in the mice model and our results may contribute to further mechanism studies based on the modern biotechnologies developed in the mice model.…”

Effective combination of aligned nanocomposite nanofibers and human unrestricted somatic stem cells for bone tissue engineering

“…Many researchers have shown that protein adsorption is an important determinant of cell adhesion in early phases. Also, initial cell adhesion is critical for the functional improvement of anchorage-dependent cells because it mediates subsequent cellular responses, including proliferation and differentiation [3,[44][45][46][47] . In this study, our main objective was to evaluate the influence of nHA on osteogenic induction in USSCs.…”

rFN/Cad-11-Modified Collagen Type II Biomimetic Interface Promotes the Adhesion and Chondrogenic Differentiation of Mesenchymal Stem Cells

“…Mimetic peptides, such as those containing the GlyPhe-hydroxyproline-Gly-Glu-Arg (GFOGER) and Asp-GlyGlu-Ala (DGEA) motifs of collagen, mediate the functions of integrin subtypes in the non-RGD pathway. 42 Although polypeptides and mimetic peptides both reasonably promote the adhesion of cells onto material surfaces, they have limited function in the chondrogenic differentiation of seed cells. In this study, we used a heterologous chimeric fusion protein (rFN/Cad-11) that was designed to cover FNIII7-10 and the FIG.…”