Inhibition of protein-tyrosine phosphatase 1B phosphorylation enhances early adhesion of mesenchymal stem cells to facilitate fabrication of tissue-engineered bone.

Abstract

Enhancement of cell-matrix adhesion is preferable and crucial in various fields of tissue engineering. Integrins are important receptors that facilitate cell-matrix adhesion, mediated by intracellular molecules and crosstalk with the cadherin adhesion pathway, which mainly facilitates cell-cell adhesion. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as a pivot in the crosstalk between the cadherin adhesion pathway and the integrin adhesion pathway. The phosphorylation state of PTP1B tyrosine-152 (Y152) plays a central role in balancing the two different cell adhesion forms. In this study, a PTP1B Y152 region mimicking (152RM) peptide was designed to decrease the phosphorylation of PTP1B Y152 via competitive inhibition. As a result, the dissociation of cadherin complexes and the release of PTP1B from cadherin had sharply increased, and Src, an important intracellular component of integrin, was activated, indicating that the cadherin adhesion pathway was inhibited, whereas the integrin adhesion pathway was enhanced. Moreover, upon treatment with the 152RM peptide, we observed that the early adhesion of human bone marrow-derived mesenchymal stem cells (MSCs) was accelerated and the anchoring of MSCs on the surface of integrin ligands was enhanced by an enhanced matrix adhesion ability of MSCs themselves. Importantly, the 152RM peptide significantly promoted the adhesion efficiency of MSCs in the selective cell retention technology, which fabricates instant bone implants in clinical settings, to stimulate osteogenesis in vivo.