Delta样非经典Notch配体2通过Notch1信号通路抑制骨髓间充质干细胞的软骨形成分化和细胞增殖。

Delta like Non-Canonical Notch Ligand 2 inhibits chondrogenic differentiation and cell proliferation of bone marrow mesenchymal stem cells through the Notch1 signaling pathway.

作者信息

Chen Yanan, Liu Yaru, Zhang Renbo, Mao Yanjie, He Axiang, Liu Wanjun

机构信息

College of Food Sciences &Technology, Shanghai Ocean University, Shanghai, China; Department of Orthopedics, Shanghai Sixth People's Hospital, Shanghai, China.

Department of Orthopedics, Shanghai Sixth People's Hospital, Shanghai, China.

出版信息

Tissue Cell. 2023 Dec;85:102220. doi: 10.1016/j.tice.2023.102220. Epub 2023 Sep 12.

DOI:10.1016/j.tice.2023.102220

Abstract

Bone marrow mesenchymal stem cells (BMSCs) is the candidate for the treatment of cartilage defects because of their directional induction potential and natural anti-inflammatory properties. As one of the non-canonical receptors of Notch1, Delta Like Non-Canonical Notch Ligand 2 (DLK2) involves in stem cells' adipogenesis and chondrogenic differentiation. However, the specific regulatory mechanism of DLK2 in the chondrogenic differentiation of BMSCs is still unclear. In this study, we found that the expression of DLK2 was reduced and the expression of Col2a1, Col10a1, Acan, Sox9, and Notch1 was raised in the process of BMSCs chondrogenic differentiation. However, the expression of Col2a1, Col10a1, Acan, and Sox9 reduced significantly, and the signal factor Notch1 and the chondrogenic differentiation capacity of BMSCs turned down in the DLK2 overexpression group. Furthermore, the expression of Col2a1, Col10a1, Acan, and Sox9 significantly enhanced, Notch1 expression was also increased, and the chondrogenic differentiation capacity of BMSCs turned up in the DLK2 suppression group. Concurrently, the proliferation of BMSCs was weakened after overexpression of DLK2, and there was no significant change in cell migration. However, the proliferation and migration of BMSCs were significantly enhanced after the inhibition of DLK2 expression. Therefore, these results suggest that DLK2 negatively regulates chondrogenic differentiation and cell proliferation in BMSCs by inhibiting the Notch1 signaling pathway.

摘要

骨髓间充质干细胞（BMSCs）因其定向诱导潜能和天然抗炎特性，成为治疗软骨缺损的候选细胞。作为Notch1的非经典受体之一，Delta样非经典Notch配体2（DLK2）参与干细胞的脂肪生成和软骨分化。然而，DLK2在BMSCs软骨分化中的具体调控机制仍不清楚。在本研究中，我们发现，在BMSCs软骨分化过程中，DLK2的表达降低，而Col2a1、Col10a1、Acan、Sox9和Notch1的表达升高。然而，在DLK2过表达组中，Col2a1、Col10a1、Acan和Sox9的表达显著降低，信号因子Notch1以及BMSCs的软骨分化能力下降。此外，在DLK2抑制组中，Col2a1、Col10a1、Acan和Sox9的表达显著增强，Notch1表达也增加，BMSCs的软骨分化能力增强。同时，DLK2过表达后BMSCs的增殖减弱，细胞迁移无显著变化。然而，抑制DLK2表达后，BMSCs的增殖和迁移显著增强。因此，这些结果表明，DLK2通过抑制Notch1信号通路负向调节BMSCs的软骨分化和细胞增殖。