Dimethyloxalylglycine regulates osteogenesis of dental pulp stem cells through PI3K/AKT signaling pathways

  • 0Key laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiao Tong University, Xi'an 710000, China.
Tissue & cell +

|

Abstract

BACKGROUND

Dental pulp mesenchymal stem cells (DPSCs) are typically cultivated in vitro under normoxic conditions, which may adversely affect their biological functions during research and treatment. Dimethyloxalylglycine (DMOG) is a small-molecule drug that has demonstrated impressive therapeutic outcomes in conditions such as osteoporosis.

OBJECTIVE

However, the influence of DMOG on the osteogenesis associated with DPSCs remains inadequately understood. We propose that DMOG may significantly impact the biological functions related to osteogenesis in DPSCs when exposed to normoxic conditions.

MATERIALS AND METHODS

DPSCs were obtained through tissue block enzyme digestion. Tube formation experiment was conducted, quantitative polymerase chain reaction (qPCR) was employed to assess the angiogenic activity of DPSCs. Additionally, alkaline phosphatase (ALP) activity tests, alizarin red staining (ARS), qPCR and western blotting (WB) assays were utilized to evaluate the osteogenic activity of DPSCs. The proposed mechanism was confirmed through repeated experiments.

RESULTS

DMOG significantly influences the osteogenic functions of DPSCs under normoxic conditions. Our findings further confirm that DMOG stimulates the phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (AKT) signaling pathway in DPSCs via phosphorylation. Inhibition of this pathway can partially impede the biological effects of DPSCs related to osteogenesis and angiogenesis.

CONCLUSION

We have addressed the gap in understanding the effect of DMOG on the osteogenesis of DPSCs. Unlike previous studies that examined the regulation of osteogenesis in stem cells by DMOG, our findings suggest that a lower dose of DMOG is sufficient to enhance the osteogenesis of DPSCs. This could represent a promising strategy for cellular therapy in bone regeneration.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply 01:24

2.5K

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...

PI3K/mTOR/AKT Signaling Pathway 01:22

3.4K

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...

Role Of Notch Signalling In Intestinal Stem Cell Renewal 01:12

2.1K

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...