Quercetin regulates ERα mediated differentiation of BMSCs through circular RNA

Circular RNA (circRNA) participates in regulation of gene transcription, while estrogen receptor alpha (ER alpha) and quercetin (QUE) positively regulate bone formation, but little is known about the correlation among circRNA, ER alpha and QUE. In this experiment, we created an ER alpha-deficient rBMSC model treated with QUE and evaluated the effects of ER alpha or QUE on rBMSCs, then analyzed differentially-expressed circRNAs by RNA-Seq and bioinformatics. The results showed that ER alpha deficiency constrained osteogenic differentiation and stimulated adipocytic differentiation of rBMSCs, while QUE abrogated those effects. We identified 136 differentially-expressed circRNAs in the Lv-shER alpha group and 120 differentially-expressed circRNAs in the Lv-shER alpha + QUE group. Thirty-two circRNAs retroregulated by ER alpha and QUE were involved in Rap1 and Wnt signaling, and four of them together sponged miR-326-5p, the target genes of which are osteogenic and adipogenic differentiation factors. Further study showed that over-expressed miR-326-5p could stimulate osteogenic differentiation, while attenuating adipogenic differentiation of rBMSCs. Therefore, we concluded that ER alpha and QUE might regulate the differentiation of rBMSCs through the circRNA-miR-326-5p-mRNA axis.