MiR-26b-3p regulates osteoblast differentiation via targeting estrogen receptor α

Background: Understanding of the molecular mechanisms of miRNAs involved in osteoblast differentiation is important for the treatment of bone-related diseases. Methods: MC3T3-E1 cells were induced to osteogenic differentiation by culturing with bone morphogenetic protein 2 (BMP2). After transfected with miR-26b-3p mimics or inhibitors, the osteogenic differentiation of MC3T3-E1 cells was detected by ALP and ARS staining. Cell viability was analyzed by MTT. The expressions of miR-26b-3p and osteogenic related markers and signaling were examined by qPCR and western blot. Direct binding of miR-26b-3p and ER-alpha were determined by dual luciferase assay. Results: miR-26b-3p was significantly down-regulated during osteoblast differentiation. Overexpression of miR-26b-3p inhibited osteoblast differentiation, while inhibition of miR-26b-3p enhanced osteoblast differentiation. Further studies demonstrated miR-26b-3p inhibited the expression of estrogen receptor a (ER-alpha) by directly targeting to the CDS region of ER-alpha mRNA. Overexpression of ER-alpha rescued the suppression effects of miR-26b-3p on osteoblast differentiation, while knockdown of ER-alpha reversed the upregulation of osteoblast differentiation induced by knockdown of miR-26b-3p. Conclusion: Our study demonstrates that miR-26b-3p suppresses osteoblast differentiation of MC3T3-E1 cells via directly targeting ER-alpha.