Glucocorticoid-induced leucine zipper may play an important role in icariin by suppressing osteogenesis inhibition induced by glucocorticoids in osteoblasts

Abstract Background and purpose Icariin is a potent stimulator of osteogenic differentiation; however, the mechanism underlying its osteogenic effect remains unclear. The osteogenic effect of icariin is related to the upstream glucocorticoid-induced leucine zipper (GILZ) signaling pathway, and antagonism with dexamethasone-induced osteoblast inhibition was noted. Methods MC3T3-E1 cells were cultured in induced medium treated with icariin with or without dexamethasone. After short interfering RNA (siRNA) were used to silence GILZ expression, the degree of mineralization, proliferation, and GILZ expression as well as the levels of osteogenic (OPG, RANKL, ALP, OC and RUNX2) markers were tested. Results Dexamethasone inhibited, while icariin increased, osteogenic activity, as indicated by ALP activity and calcium nodules. Meanwhile, dexamethasone dose-dependently (10 −6  M–10 −4  M) increased GILZ and RANKL expression and reduced ALP, OPG and OC, but the pattern of mRNA expression was reversed when icariin was added. Furthermore, GILZ (dexamethasone-induced) inhibition caused by icariin or moderately silenced by GILZ siRNA abolished the osteogenesis inhibition effect of dexamethasone, as indicated by the changes in the GILZ, ALP, OPG and RANKL expression levels; ALP activity; and calcium nodule. Conclusions These results indicate that the GILZ-mediated osteogenic signal pathway is involved in the osteogenic effect induced by icariin.