Undercarboxylated Osteocalcin Increases the Dopaminergic Activity of Neuronal Differentiated PC12 Cells In Vitro

Background/Purpose: Dysfunctions in the neurotransmitter metabolism of dopamine and noradrenaline are an important factor in pathogenesis of many psychiatric and neurological diseases, such as Parkinson's disease or attention deficit hyperactivity disorder. Recent findings indicate that uncarboxylated osteocalcin (ucOCN), a hormone released by bone tissue, crosses the blood–brain barrier and influences the neurotransmitter balance. Our study examined ucOCN's impact on the catecholamine metabolism of PC12 cells, a neuronal differentiated cell line in vitro.

Methods: First PC12 cells were tested for their expression of the G-protein coupled receptor 158 (GPR158). Secondary they were incubated with ucOCN for 24 or 48 hours. The effect was determined by means of the gene expression of selected enzymes and transporters involved in the catecholamine metabolism as well as by the extracellular dopamine concentration in culture supernatant of either spontaneous transmitter release or after cellular excitation by potassium chloride.

Results: On protein level GPR158 was expressed along the cell surface of PC12 cells. Simulation for 48 hours with 100 ng/mL ucOCN resulted in a significant increase of extracellular dopamine concentration by 22.7%, while the gene expression was unchanged.

Conclusion: Stimulation of PC12 cells with ucOCN resulted in a small but significant increase of their dopaminergic activity. Further in vitro studies using PC12 cells could help to validate the effects found and provide deeper insight into potential impact of ucOCN on neurotransmission. This knowledge might result in ideas for new preventive or therapeutic applications of ucOCN.

Publication History

Article published online:
28 October 2021