Mesenchymal Stem Cells and Osteoblast Function: Investigating the Involvement of circGLIS2

Osteoporosis (OP) is a prevalent physiological bone disorder that attribute to elevated bone absorption and disrupted bone formation. Accumulating evidence has reported that epigenetic modifications may participate in mechanisms of OP. In this work, we aimed at determining the expression pattern and effects of circular RNA GLIS2 on OP. The concentrations of circGLIS2, miR-214-3p, and Smad5 in clinical samples of OP patients and healthy donors were quantified by qRT-PCR. Human bone marrow stem cells (BMSCs) were stimulated with osteogenic medium to promote bone development. The protein expression of osteogenic biomarkers, such asosteocalcin (OCN) and osteopontin (OPN), were assessed with western blotting. The expression of circGLIS2 and Smad5 were decreased and miR-214-3p values was elevated in clinical specimens of OP patients in comparison with the healthy donors. The expression of circGLIS2 was notably elevated in BMSCs upon osteogenic differentiation. Knockdown of circGLIS2 notably suppressed the OPN and OCN levels, decreased the ALP activity and the Alizarin Red S staining. Overexpression of Smad5 and inhibition of miR-214-3p could recover the suppressed osteogenic differentiation that caused by circGLIS2 depletion. In conclusion, circGLIS2 sponges miR-214-3p to upregulate Smad5, the which enhanced osteogenic differentiation of the BMSCs. Our finding provided a potential novel target for the therapeutic strategies of OP.