Cross-linking of collagen I by tissue transglutaminase provides a promising biomaterial for promoting bone healing

• Published in: Amino acids 2014-07, Vol.46 (7), p.1751-1761
• Main Authors: Fortunati, Dario, Chau, David Yi San, Wang, Zhuo, Collighan, Russell John, Griffin, Martin
• Format: Article
• Language: English
• Subjects: Adhesion; alkaline phosphatase; Alkaline Phosphatase - metabolism; Analytical Chemistry; antibodies; Antibodies - pharmacology; Biochemical Engineering; Biochemistry; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Biomedical and Life Sciences; bone morphogenetic proteins; Bones; CD29 antigen; Cell Adhesion - drug effects; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cells, Cultured; collagen; Collagen Type I - chemistry; Collagens; cross-linking; Crosslinking; Gene Expression Regulation - drug effects; GTP-Binding Proteins - chemistry; Healing; Human; Humans; Integrins - immunology; Kinases; Life Sciences; lysine; Materials Testing; Neurobiology; non-specific protein-tyrosine kinase; Oligopeptides - pharmacology; Original Article; osteoblasts; Osteoblasts - drug effects; peptides; Peptides - chemistry; Peptides - pharmacology; phosphorylation; protein-glutamine gamma-glutamyltransferase; Proteins; Proteomics; rheological properties; Signal Transduction - drug effects; Transglutaminases - chemistry
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-014-1732-0

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.