alpha_2beta_1 Integrin-specific collagen-mimetic surfaces supporting osteoblastic differentiation

摘要

The interactions of osteoblasts with their surrounding extracellular matrix (ECM) are essential for skeletal development, homeostasis, and maintenance of the mature osteoblastic phertotype. Integrins are the principal transducers of ECM signals that regulate this process of osteoblast commitment and differentiation. Several studies indicate that the alpha_2beta_1 integrin interaction with type I collagen is a crucial signal for the induction of osteoblastic differentiation and matrix mineralization. Integrin alpha_2beta_1 recognizes the Gly-Phe-Hyp-Gly-Glu-Arg (GFOGER). motif in residues 502-507 of the alpha_1[l] chain of type I collagen. This study demonstrates that an alpha_2beta_1 integrin-spedfic GFOGER peptide triggers the activation of focal adhesion kinase and alkaline phosphatase in MC3T3-E1 murine immature osteoblast-like cells, two events that have been implicated in the osteoblastic differentiation pathway. These GFOGER-pep-tide surfaces also support the expression of multiple osteoblast-specific genes, including osteocalcin and bone sialo-protein, and induce matrix mineralization in a manner similar to type I collagen. This triple-helical peptide represents a promising surface modification strategy for the design of collagen-mimetic bioadhesive surfaces that support osteoblastic differentiation.