Cross-linking of collagen I by tissue transglutaminase provides a promising biomaterial for promoting bone healing.
Transglutaminases (TGs) stabilize proteins by the formation of ε(γ-glutamyl)lysine cross-links. Here, we demonstrate that the cross-linking of collagen I (COL I) by tissue transglutaminase (TG2) causes an alteration in the morphology and rheological properties of the collagen fibers. Human osteoblasts (HOB) attach, spread, proliferate, differentiate and mineralize more rapidly on this cross-linked matrix compared to native collagen. When seeded on cross-linked COL I, HOB are more resistant to the loss of cell spreading by incubation with RGD containing peptides and with α1, α2 and β1 integrin blocking antibodies. Following adhesion on cross-linked collagen, HOB show increased phosphorylation of the focal adhesion kinase, and increased expression of β1 and β3 integrins. Addition of human bone morphogenetic protein to HOB seeded on TG2 cross-linked COL I enhanced the expression of the differentiation marker bone alkaline phosphatase when compared to cross-linked collagen alone. In summary, the use of TG2-modified COL I provides a promising new scaffold for promoting bone healing.
School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK.
Dario
D
Fortunati
David Yi San
DY
Chau
Zhuo
Z
Wang
Russell John
RJ
Collighan
Martin
M
Griffin
D000469:Alkaline Phosphatase / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000737:chemistry*; D019204:GTP-Binding Proteins / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016023:Integrins / Q000276:immunology; D008422:Materials Testing; D009842:Oligopeptides / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015398:Signal Transduction / Q000187:drug effects; D011503:Transglutaminases / Q000737:chemistry*
D000906:Antibodies; D001672:Biocompatible Materials; D024042:Collagen Type I; D016023:Integrins; D009842:Oligopeptides; D010455:Peptides; C047981:arginyl-glycyl-aspartic acid; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D000469:Alkaline Phosphatase; D019204:GTP-Binding Proteins