AUTHOR=Yu Wei , Chen Fan-Cheng , Xu Wen-Ning , Ding Sheng-Long , Chen Peng-Bo , Yang Lei , Jiang Sheng-Dan , Pan Xiao-Yun 

TITLE=Inhibition of Y1 Receptor Promotes Osteogenesis in Bone Marrow Stromal Cells via cAMP/PKA/CREB Pathway

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.583105

DOI=10.3389/fendo.2020.583105

ISSN=1664-2392

ABSTRACT=<p>Inhibition of neuropeptide Y1 receptor stimulates osteogenesis <italic>in vitro</italic> and <italic>in vivo</italic>. However, the underlying mechanisms involved in these effects remain poorly understood. Here we identify the effects of Y1 receptor deficiency on osteogenic differentiation in human bone marrow stromal cells (BMSCs) by using genetic and pharmacological regulation, and to explore the pathways mediating these effects. In BMSCs, inhibition of Y1 receptor stimulates osteogenesis and upregulates the expression levels of the master transcriptional factor RUNX2. Mechanistically, Y1 receptor deficiency increases the levels of intracellular cAMP, which <italic>via</italic> protein kinase A (PKA) mediated pathways results in activation of phospho-CREB (p-CREB). We find RUNX2 activation induced by Y1 receptor deficiency is reversed by H-89, a PKA inhibitor. These results indicate Y1 receptor deficiency activates PKA-mediated phosphorylation of CREB, leading to activation of RUNX2 and enhances osteogenic differentiation in BMSCs. In conclusion, these data indicate that Y1 receptor deficiency promotes osteogenic differentiation by RUNX2 stimulation through cAMP/PKA/CREB pathway.</p>