2023 Volume No 45 – pages 14-30
Title: GRP78 promotes the osteogenic and angiogenic response in periodontal ligament stem cells |
Authors: A Merkel, Y Chen, C Villani, A George |
Address: Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA |
E-mail: anneg at uic.edu |
Abstract: Periodontitis is a progressive disease that ultimately leads to bone and tooth loss. A major consequence of
periodontal disease is the inability to regain lost bone in the periodontium. The importance was demonstrated
of glucose-regulated protein-78 (GRP78) in the osteogenic differentiation of periodontal ligament stem cells and
their potential use for regeneration of the periodontium. Previous studies have shown the relationship between
GRP78 and dentine matrix protein-1 (DMP1). The importance of this receptor-ligand complex in supporting
the process of osteogenesis and angiogenesis was confirmed in this study. To show the function of GRP78 in
mineralised tissues, transgenic periodontal ligament stem cells (PDLSCs) were generated in which GRP78 was
either overexpressed or silenced. Gene expression analysis of the cells cultured under osteogenic conditions
showed an increase in key osteogenic genes with the overexpression of GRP78. RNA-Seq analysis was also
performed to understand the transcriptome profile associated with genotype changes. Using the database
for annotation, visualisation, and integration discovery (DAVID) for the functional enrichment analysis of
differentially expressed genes, the upregulation of genes promoting osteogenesis and angiogenesis with
GRP78 overexpression was demonstrated. Alizarin red staining and scanning electron microscopy analysis
revealed matrix mineralisation with increased calcium deposition in GRP78 overexpressing cells. The in vivo
osteogenic and angiogenic function of GRP78 was shown using a subcutaneous implantation rodent model.
The results suggested that GRP78 in PDLSCs can regulate the expression of both osteogenesis and angiogenesis.
Therefore, GRP78 could be considered as a therapeutic target for repair of diseased periodontium. |
Keywords: Stem cells, tissue engineering, periodontal disease, GRP78, osteoblastogenesis, angiogenesis. |
Publication date: January 23rd 2023 |
Article download: Pages
14-30 (PDF file) |
