Novel Molecule Nell-1 Promotes the Angiogenic Differentiation of Dental Pulp Stem Cells

Front Physiol. 2021 Aug 26:12:703593. doi: 10.3389/fphys.2021.703593. eCollection 2021.

Abstract

Introduction: This work aimed to reveal the crucial role of Nell-1 in the angiogenic differentiation of human dental pulp stem cells (DPSCs) alone or co-cultured with human umbilical vein endothelial cell (HUVECs) in vitro and whether this molecule is involved in the pulp exposure model in vivo.

Methods: Immunofluorescence was conducted to ascertain the location of Nell-1 on DPSCs, HUVECs, and normal rat dental tissues. RT-PCR, Western blot, and ELISA were performed to observe the expression levels of angiogenic markers and determine the angiogenic differentiation of Nell-1 on DPSCs alone or co-cultured with HUVECs, as well as in vitro tube formation assay. Blood vessel number for all groups was observed and compared using immunohistochemistry by establishing a rat pulp exposure model.

Results: Nell-1 is highly expressed in the nucleus of DPSCs and HUVECs and is co-expressed with angiogenic markers in normal rat pulp tissues. Hence, Nell-1 can promote the angiogenic marker expression in DPSCs alone and co-cultured with other cells and can enhance angiogenesis in vitro as well as in the pulp exposure model.

Conclusion: Nell-1 may play a positive role in the angiogenic differentiation of DPSCs.

Keywords: angiogenesis; human dental pulp cells; human umbilical vein endothelial cells; nel-like molecule-1; pulp regeneration.