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

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.