Oxytocin Modulates Osteogenic Commitment in Human Adipose-Derived Stem Cells

Abstract

Human adipose-derived stem cells (hASCs) are commonly harvested in minimally invasive contexts with few ethical concerns, and exhibit self-renewal, multi-lineage differentiation, and trophic signaling that make them attractive candidates for cell therapy approaches. The identification of natural molecules that can modulate their biological properties is a challenge for many researchers. Oxytocin (OXT) is a neurohypophyseal hormone that plays a pivotal role in the regulation of mammalian behavior, and is involved in health and well-being processes. Here, we investigated the role of OXT on hASC proliferation, migratory ability, senescence, and autophagy after a treatment of 72 h; OXT did not affect hASC proliferation and migratory ability. Moreover, we observed an increase in SA-β-galactosidase activity, probably related to the promotion of the autophagic process. In addition, the effects of OXT were evaluated on the hASC differentiation ability; OXT promoted osteogenic differentiation in a dose-dependent manner, as demonstrated by Alizarin red staining and gene/protein expression analysis, while it did not affect or reduce adipogenic differentiation. We also observed an increase in the expression of autophagy marker genes at the beginning of the osteogenic process in OXT-treated hASCs, leading us to hypothesize that OXT could promote osteogenesis in hASCs by modulating the autophagic process.

Investigation on the Oxytocin Effect on Proliferation and Osteogenic/Odontogenic Differentiation of Human Stem Cells from the Apical Papilla: An in vitro study

“…Consistent with our study, they showed that OT increases the gene expression of DSP, Wnt10a, and BGP in dental pulp stem cells.In their review study, Liu Feixiang et al(Feixiang, Yanchen et al 2023) showed that OT can stimulate osteoblast mineralization by promoting translocation of the OT receptor to the osteoblast nucleus.Additionally, by inducing intracellular Ca 2+ release and nitric oxide synthesis, OT can regulate the OPG/RANKL ratio in osteoblasts and exert a two-way regulatory effect on osteoclasts. It can also increase osteocyte and chondrocyte activity, which increase bone mass and improve bone microstructure.The present study's ndings align with previous research, indicating that OT promotes the differentiation of stem cells into osteoblasts(Elabd, Basillais et al 2008, Petrocelli, Abruzzo et al 2023).…”

“…In the Petrocelli et al (Petrocelli, Abruzzo et al 2023) study examining the effect of OT on the proliferation of adipose-derived stem cells, although OT had no cytotoxic effects on the cells, no proliferative effect was found by this agent. They showed that the expression of genes involved in cell proliferation and cell cycle including MKI67, CCND1, CDKN2A, CDKN1A, and TP53, was not affected in OT-treated cells.…”

“…OT also increased the expression of this gene on days 14 and 21 in hSCAPs. Petrocelli et al (Petrocelli, Abruzzo et al 2023) conducted a study to investigate the impact of OT on the expression of the RUNX2 gene in both osteogenic and non-differentiation media. The ndings revealed a signi cant increase in RUNX2 expression when OT was introduced in the osteogenic medium, but there were no notable changes compared to the control group in the non-differentiation medium.…”