Inhibition of protein‐tyrosine phosphatase 1B phosphorylation enhances early adhesion of mesenchymal stem cells to facilitate fabrication of tissue‐engineered bone
Inhibition of protein‐tyrosine phosphatase 1B phosphorylation enhances early adhesion of mesenchymal stem cells to facilitate fabrication of tissue‐engineered bone
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DOI：
10.1002/term.3021
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发表时间：
2020-02
影响因子：
3.3
通讯作者：
Keyu Luo;Yong Tang;Xiaoliang Gao;Jiulin Tan;Bo Yu;Jianzhong Xu;F. Luo
中科院分区：
文献类型：
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作者：
Keyu Luo;Yong Tang;Xiaoliang Gao;Jiulin Tan;Bo Yu;Jianzhong Xu;F. Luo
在组织工程的各个领域中，增强细胞与基质的黏附是可取的，也是至关重要的。整合素是促进细胞-基质黏附的重要受体，由细胞内分子介导，并与钙粘附素黏附通路串扰，主要促进细胞-细胞黏附。蛋白酪氨酸磷酸酶1B(PTP1B)是钙粘附素黏附通路和整合素黏附通路之间相互作用的枢纽。PTP1B酪氨酸152(Y152)的磷酸化状态在平衡两种不同的细胞黏附形式中起着核心作用。在本研究中，设计了一个PTP1B Y152区模拟多肽(152RM)，通过竞争抑制降低PTP1B Y152的磷酸化。结果表明，钙粘蛋白复合体的解离和PTP1B的释放急剧增加，整合素的重要胞内成分Src被激活，表明钙粘附素的黏附途径受到抑制，而整合素的黏附途径被增强。此外，经152Rm多肽处理后，我们观察到人骨髓间充质干细胞(MSCs)的早期黏附被加速，MSCs自身增强的基质黏附能力增强了MSCs在整合素配体表面的锚定。重要的是，152Rm多肽在选择性细胞保留技术中显著促进了MSCs的黏附效率，该技术在临床环境下制造即时骨移植，以刺激体内成骨。
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.