Phosphorylation Inhibition of Protein-tyrosine Phosphatase 1B Tyrosine-152 Induces Bone Regeneration Coupled with Angiogenesis for Bone Tissue Engineering

Overview

Journal Bioact Mater

Specialty Biomedical Engineering

Date 2021 Jan 29

PMID 33511306

Citations 8

Authors

Yong Tang

Keyu Luo

Yin Chen

Yueqi Chen

Rui Zhou

Can Chen

Jiulin Tan

Moyuan Deng

Qijie Dai

Xueke Yu

Jian Liu

Chengmin Zhang

Wenjie Wu

Jianzhong Xu

Shiwu Dong

Fei Luo

Affiliations

Soon will be listed here.

Abstract

A close relationship has been reported to exist between cadherin-mediated cell-cell adhesion and integrin-mediated cell mobility, and protein tyrosine phosphatase 1B (PTP1B) may be involved in maintaining this homeostasis. The stable residence of mesenchymal stem cells (MSCs) and endothelial cells (ECs) in their niches is closely related to the regulation of PTP1B. However, the exact role of the departure of MSCs and ECs from their niches during bone regeneration is largely unknown. Here, we show that the phosphorylation state of PTP1B tyrosine-152 (Y152) plays a central role in initiating the departure of these cells from their niches and their subsequent recruitment to bone defects. Based on our previous design of a PTP1B Y152 region-mimicking peptide (152RM) that significantly inhibits the phosphorylation of PTP1B Y152, further investigations revealed that 152RM enhanced cell migration partly via integrin αvβ3 and promoted MSCs osteogenic differentiation partly by inhibiting ATF3. Moreover, 152RM induced type H vessels formation by activating Notch signaling. Demineralized bone matrix (DBM) scaffolds were fabricated with mesoporous silica nanoparticles (MSNs), and 152RM was then loaded onto them by electrostatic adsorption. The DBM-MSN/152RM scaffolds were demonstrated to induce bone formation and type H vessels expansion . In conclusion, our data reveal that 152RM contributes to bone formation by coupling osteogenesis with angiogenesis, which may offer a potential therapeutic strategy for bone defects.

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