Osteogenesis from Dental Pulp Derived Stem Cells: A Novel Conditioned Medium Including Melatonin within a Mixture of Hyaluronic, Butyric, and Retinoic Acids

Abstract

Human dental pulp stem cells (hDPSCs) have shown relevant potential for cell therapy in the orthopedic and odontoiatric fields. The optimization of their osteogenic potential is currently a major challenge. Vascular endothelial growth factor A (VEGF A) has been recently reported to act as a major conductor of osteogenesis in vitro and in vivo. Here, we attempted to prime endogenous VEGF A expression without the need for viral vector mediated gene transfer technologies. We show that hDPSCs exposure to a mixture of hyaluronic, butyric, and retinoic acids (HA + BU + RA) induced the transcription of a gene program of osteogenesis and the acquirement of an osteogenic lineage. Such response was also elicited by cell exposure to melatonin, a pleiotropic agent that recently emerged as a remarkable osteogenic inducer. Interestingly, the commitment to the osteogenic fate was synergistically enhanced by the combinatorial exposure to a conditioned medium containing both melatonin and HA + BU + RA. These in vitro results suggest that in vivo osteogenesis might be improved and further studies are needed.

Methods of Isolation, Characterization and Expansion of Human Adipose-Derived Stem Cells (ASCs): An Overview

“…The osteogenic differentiation medium must contain: β-glycerophosphate, dexamethasone, ascorbic acid-2-phosphate and combinations of transforming growth factor-beta (TGF-β), bone morphogenetic proteins and vitamin D3 [ 1 , 40 ]. Recently, melatonin or a mixture of hyaluronic, butyric, and retinoic acids have been reported to efficiently promote an osteogenic patterning in human dental pulp stem cells by inducing the transcription of a gene program of osteogenesis [ 41 , 42 ]. The differentiation of ASCs into osteocytes is controlled by various transcription factors as such as Runt-related transcription factor 2 (Runx2), osterix, and β-catenin.…”

Combined Fluid Shear Stress and Melatonin Enhances the ERK/Akt/mTOR Signal in Cilia-Less MC3T3-E1 Preosteoblast Cells

“…Melatonin functions as a broad-spectrum antioxidant [ 10 , 11 , 12 ] and has anti-apoptotic and anti-autophagic effects [ 13 , 14 , 15 , 16 , 17 ]. Moreover, melatonin modulates osteogenic and adipogenic differentiation, in different kinds of mesenchymal stem cells, including dental pulp-derived stem cells and adipose-derived stem cells [ 18 , 19 ]. Recently, Kim and Yoo [ 20 ] reported that a combination of FSS and melatonin activates anabolic proteins through the p-ERK in MC3T3-E1 osteoblast cells.…”

Unravelling Cellular Mechanisms of Stem Cell Senescence: An Aid from Natural Bioactive Molecules

“…ROS have been recognized as toxic and harmful by-products for stem cells, resulting in DNA damage, premature senescence or cell death [22]. MSCs are largely known for their ability to restore tissue function and differentiate into several phenotypes under appropriate stimuli [23], including osteogenic, chondrogenic, cardiogenic and adipogenic lineages [24][25][26][27]. Nevertheless, as previously demonstrated by Liao N et al, hADSCs expanded for different passages, showing high mRNA levels of p16, p21 and p53 and an increased ROS production, associated with the appearance of a senescent phenotype.…”