Circular RNA (circRNA) participates in regulation of gene transcription, while 
estrogen receptor alpha (ERα) and quercetin (QUE) positively regulate bone 
formation, but little is known about the correlation among circRNA, ERα and QUE. 
In this experiment, we created an ERα-deficient rBMSC model treated with QUE and 
evaluated the effects of ERα or QUE on rBMSCs, then analyzed 
differentially-expressed circRNAs by RNA-Seq and bioinformatics. The results 
showed that ERα deficiency constrained osteogenic differentiation and stimulated 
adipocytic differentiation of rBMSCs, while QUE abrogated those effects. We 
identified 136 differentially-expressed circRNAs in the Lv-shERα group and 120 
differentially-expressed circRNAs in the Lv-shERα + QUE group. Thirty-two 
circRNAs retroregulated by ERα 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 
ERα and QUE might regulate the differentiation of rBMSCs through the 
circRNA-miR-326-5p-mRNA axis.