PTPN21 Overexpression Promotes Osteogenic and Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells but Inhibits the Immunosuppressive Function
PTPN21 Overexpression Promotes Osteogenic and Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells but Inhibits the Immunosuppressive Function
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PTPN21过表达促进骨髓间充质干细胞的成骨和脂肪分化，但抑制免疫抑制功能
DOI：
10.1155/2019/4686132
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发表时间：
2019-11
影响因子：
4.3
通讯作者：
Huang He
中科院分区：
文献类型：
--
作者：
Wang Huafang;Ye Xiaohang;Xiao Haowen;Zhu Ni;Wei Cong;Sun Xiang;Wang Limengmeng;Wang Binsheng;Yu Xiaohong;Lai Xiaoyu;Fu Shan;Huang He
蛋白质酪氨酸磷酸酶（PTPs）在增殖、分化和迁移等各种细胞过程中充当关键调节因子。我们的前期研究表明，非受体型PTP 21（PTPN 21），PTP家族的成员，在急性淋巴细胞白血病细胞的增殖，细胞周期和化疗敏感性中起着关键作用。然而，PTPN 21在骨髓微环境中的作用尚未阐明。本研究通过慢病毒介导的PTPN 21过表达和敲低，探讨PTPN 21对体外培养的人骨髓间充质干细胞（BM-MSCs）的影响。过表达PTPN 21的骨髓间充质干细胞可将细胞周期阻滞在G 0期，从而抑制细胞增殖，但其成骨和成脂分化能力增强。此外，在BM-MSC中过表达PTPN 21通过上调P21和P53增加了它们的衰老水平，并显著改变了与它们的典型靶细胞（包括免疫细胞、肿瘤细胞和血管内皮细胞）的串扰水平。PTPN 21过表达的骨髓间充质干细胞在趋化性transwell共培养系统中免疫抑制功能受损，招募肿瘤细胞和血管内皮细胞的能力增加。总之，我们的数据表明，PTPN 21作为一个多效性因子在调节人BM-MSCs的功能。
Protein tyrosine phosphatases (PTPs) act as key regulators in various cellular processes such as proliferation, differentiation, and migration. Our previous research demonstrated that non-receptor-typed PTP21 (PTPN21), a member of the PTP family, played a critical role in the proliferation, cell cycle, and chemosensitivity of acute lymphoblastic leukemia cells. However, the role of PTPN21 in the bone marrow microenvironment has not yet been elucidated. In the study, we explored the effects of PTPN21 on human bone marrow-derived mesenchymal stem cells (BM-MSCs) via lentiviral-mediated overexpression and knock-down of PTPN21 in vitro. Overexpressing PTPN21 in BM-MSCs inhibited the proliferation through arresting cell cycle at the G0 phase but rendered them a higher osteogenic and adipogenic differentiation potential. In addition, overexpressing PTPN21 in BM-MSCs increased their senescence levels through upregulation of P21 and P53 and dramatically changed the levels of crosstalk with their typical target cells including immunocytes, tumor cells, and vascular endothelial cells. BM-MSCs overexpressing PTPN21 had an impaired immunosuppressive function and an increased capacity of recruiting tumor cells and vascular endothelial cells in a chemotaxis transwell coculture system. Collectively, our data suggested that PTPN21 acted as a pleiotropic factor in modulating the function of human BM-MSCs.
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影响因子：
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作者：
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影响因子：
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