The mechanism of oxytocin and its receptors in regulating cells in bone metabolism

Abstract

Oxytocin (OT) is a neuropeptide known to affect social behavior and cognition. The epigenetic modification of the oxytocin receptor (OTR) via DNA methylation stimulates parturition and breast milk secretion and inhibits craniopharyngioma, breast cancer, and ovarian cancer growth significantly as well as directly regulates bone metabolism in their peripheral form rather than the central form. OT and OTR can be expressed on bone marrow mesenchymal stem cells (BMSCs), osteoblasts (OB), osteoclasts (OC), osteocytes, chondrocytes, and adipocytes. OB can synthesize OT under the stimulation of estrogen as a paracrine–autocrine regulator for bone formation. OT/OTR, estrogen, and OB form a feed-forward loop through estrogen mediation. The osteoclastogenesis inhibitory factor (OPG)/receptor activator of the nuclear factor kappa-B ligand (RANKL) signaling pathway is crucially required for OT and OTR to exert anti-osteoporosis effect. Downregulating the expression of bone resorption markers and upregulating the expression of the bone morphogenetic protein, OT could increase BMSC activity and promote OB differentiation instead of adipocytes. It could also stimulate the mineralization of OB by motivating OTR translocation into the OB nucleus. Moreover, by inducing intracytoplasmic Ca2+ release and nitric oxide synthesis, OT could regulate the OPG/RANKL ratio in OB and exert a bidirectional regulatory effect on OC. Furthermore, OT could increase the activity of osteocytes and chondrocytes, which helps increase bone mass and improve bone microstructure. This paper reviews recent studies on the role of OT and OTR in regulating cells in bone metabolism as a reference for their clinical use and research based on their reliable anti-osteoporosis effects.

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

“…Falahnezhad et al(Fallahnezhad, Piryaei et al 2018) showed that OT signi cantly increased ALP activity in bone marrow stem cells at 7, 14, and 21 days. Liu Feixiang et al(Feixiang, Yanchen et al 2023) proposed that OT induces osteoblasts differentiation and mineralization by promoting OTR translocation into the nucleus. OT may also modulate the OPG/RANKL ratio in osteoblasts by eliciting intracellular Ca 2+ release and nitric oxide production, thereby exerting regulatory effects on osteoclasts.…”

“…Yuka Kato et al(Kato and Yokose 2021) demonstrated that in addition to odontoblasts and periodontal ligament cells, the OT receptor is also expressed in dental pulp stem cells. 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).…”